voltage-dependent L-type calcium channel

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Voltage dependent calcium channels: Subcellular subunit localisation and targeting

Voltage dependent calcium channels: Subcellular subunit localisation and targeting

The a i e clone is the counterpart of the L-type channel found most predominantly in cardiac tissue, although it has also been detected in a number of tissues including brain, (Snutch et a/. 1991) lung (Biel et a/. 1990) and kidney (Yu, 1995). It has a 66% overall homology to the a l S subunit and a predicted molecular mass o f 243kDa. There are at least six sites for alternative splicing reported in the a lC subunit, the amino terminus, IS6, cytoplasmic loop between IS6 and IISl, IIIS2, IVS3 (and flanking regions) and cytoplasmic C-terminal tail (Perez-Reyes et a l 1994) and a site o f proteolytic cleavage of the C-terminal tail. It is not yet clear if the variants are tissue specific, although the long amino terminal isoform appears to be dominant in the heart (Biel et a l 1991). The fimctional significance o f all the variants is even less well understood. It is known that different isoforms have different phosphorylation sites but differences in current kinetics are not always observed. Klockner et a l (1997) found three message variants for the C-terminal region of the human cardiac a 1C, although little change in electrophysiological properties. In contrast, Soldatov et a l (1997) showed significant increase in current inactivation and a current-voltage (I-V) shift to more hyperpolarised potentials, for one of three a lC subunits with alternatively spliced C-terminal tails isolated from human hippocampus. It is not clear if these are similar to those variants isolated by Klockner and colleagues. Welling et a l (1993) showed a difference in the pharmacology of the L-type current from the heart and the lung for the DHP antagonist, nisoldipine, although little is known about the structure of the lung a lC in this case. In light of the proposed second p binding site at the C- terminal (Qin et a l 1997; Walker et a l 1998) (See section 1.6.2) it remains a possibility that these splice variants may also alter the interaction between a l and P, alternatively they may determine subunit targeting or signalling.
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Pharmacological and biophysical characteristics of voltage-dependent calcium channels in rat cerebellar granule neurones

Pharmacological and biophysical characteristics of voltage-dependent calcium channels in rat cerebellar granule neurones

Diversity is also shown by studies of single calcium channels in cerebellar granule neurones. Pietrobon’s group have shown distinct DHP-sensitive L-type channels, one displaying sporadic short openings with a low open channel probability which are prolonged in the presence of DHP agonist, have an inactivating profile and showing a high number of nulls. The other showed fast, unresolved openings, which in the presence of DHP agonist were resolved as short 2 ms openings and long closings, non-inactivating, with a lesser proportion of null sweeps (Forti and Pietrobon, 1993). P- and R-type channels were also shown to be functionally diverse. Three distinct channels were identified, each having a characteristic conductance and activation threshold, but similar inactivation having both an inactivating and a non-decaying component (Forti et al, 1994). Later studies (Tottene et al, 1996) showed by pharmacological criteria that one of these channels could be classified as a novel P-type channel, being insensitive to co- CgTx G VIA and nimodipine, but blocked by co-Aga TVA (saturating at 50 nM) and ci>CTx MVnC, yet showing complete voltage-dependent inactivation at potentials having no effect on currents in Purkinje cells. The two remaining channels were both insensitive to all calcium channel blockers and displayed voltage-dependent properties similar to LVA channels. Similarities were apparent to the R-type current described by Randall and Tsien (1995) in that Ni^"^ could block the residual current in whole-cell recordings with a biphasic concentration- dependence with dissociation constants calculated to be 12 pM and 286 pM
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Voltage gated calcium channel currents in human coronary myocytes  Regulation by cyclic GMP and nitric oxide

Voltage gated calcium channel currents in human coronary myocytes Regulation by cyclic GMP and nitric oxide

after enzymatic dissociation and after primary culture of coronary myocytes taken from heart transplant patients. We recorded a dihydropyridine-sensitive L-type current in both freshly isolated and primary cultured cells. A T-type current was recorded only in culture. The L- (but not the T-) type current was inhibited by permeable analogues of cGMP in a dose-dependent manner. This effect was mim- icked by the nitric oxide–generating agents S -nitroso- N -ace- tylpenicillamine (SNAP) and 3-morpholinosydnonimine which increased intracellular cGMP. Methylene blue, known to inhibit guanylate cyclase, antagonized the effect of SNAP. Inhibitions by SNAP and cGMP were not additive and seemed to occur through a common pathway. We con- clude that ( a ) L-type Ca 2 1 channels are the major pathway
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Shaltiel, Lior
  

(2013):


	In vivo and in vitro analysis of the retinal voltage dependent L-type Ca2+channel Ca 1.4 function.


Dissertation, LMU München: Fakultät für Chemie und Pharmazie

Shaltiel, Lior (2013): In vivo and in vitro analysis of the retinal voltage dependent L-type Ca2+channel Ca 1.4 function. Dissertation, LMU München: Fakultät für Chemie und Pharmazie

Intracellular calcium signals are essential for a variety of physiological processes (Berridge, 2004; Catterall, 2010; Turner et al., 2011). They affect virtually all cellular processes, from the excitation-contraction coupling in skeletal and cardiac muscles through signal transduction, hormone and neurotransmitter release, regulation of enzyme activity, gene expression to cell proliferation in different cell types. These signals are generated when calcium enters the cell via voltage gated Ca 2+ channels in the plasma membrane. Alternatively, intracellular Ca 2+ can transiently rise upon release from intracellular organelles such as ER, nuclear envelop, mitochondria and lysosomes. Voltage gated Ca 2+ channels in the plasma membrane belong to the superfamily of voltage gated pore loop ion channels. This superfamily also includes voltage-gated sodium and potassium channels. Voltage gated Ca 2+ channels open in response to changes in the membrane potential. The opening and the closing of these calcium channels is regulated by hormones, protein kinases, protein phosphatases, and drugs (Hofmann et al., 1999; Minor and Findeisen, 2010). Changes in the function and expression of calcium channels lead to cellular disorders and thereby a number of diseases (Bidaud et al., 2006; Striessnig et al., 2010).
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Genetic and physical mapping of the murine epilepsy locus lethargic (lh) and investigation of voltage-dependent calcium channel beta subunits in human absence seizure predisposition

Genetic and physical mapping of the murine epilepsy locus lethargic (lh) and investigation of voltage-dependent calcium channel beta subunits in human absence seizure predisposition

Currently seven human and two mouse disorders have been shown to be due to m utations in the a i pore form ing subunit. Interestingly, all five m utations of the ajA isoform have been shown to predispose paroxysmal cerebella dysfunction and ataxia, w hilst the three displaying m utation in the a is isoform result in m uscle loss, rigidity or atonia (Figure 1.6.5). The affected tissues seen in these diseases m irror closely the predom inant expression patterns previously described for each subunit (Table 1.6.2). A positional cloning investigation in the mouse identified disease causing m utations in the aiA pore form ing subunit, C acnala, underlying the tottering allele, tg (Fletcher et a l , 1996; D oyle et al., 1997) and tg^'' phenotypes (Fletcher et al., 1996). A ssignm ent of the hum an ajA subunit gene, C AC N A IA, to chrom osom e 1 9 p l3 .2-13.1 also showed the gene to co-localise with a locus for hum an fam ilial hem iplegic m igraine (O phoff et al., 1996) and episodic ataxia type 2 disorders (O phoff et al.,
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Expression, characterisation and structural analysis of the putative slow voltage-dependent potassium channel minK

Expression, characterisation and structural analysis of the putative slow voltage-dependent potassium channel minK

Heterologous expression o f proteins in the yeast Saccharom yces cerevisiae, a simple eukaryote, has many o f the same advantages as E. coli. The genetics and physiology o f S. cerevisiae have been well characterised, and like E. coli, it can grow in simple defined media, has a rapid growth rate yielding very high densities and can be transfected with a wide variety o f self-replicating vectors. Yeasts allow integration o f vector D N A into a specific site in their genome ensuring stability and maintenance o f the vector in the transfected cells (Siest et a i , 1993). Because D N A manipulations are easier in E. coli, yeast vectors are designed as shuttle vectors containing additional elements that allow for its selection and propagation in bacteria. Vectors are available with a variety o f inducible promoters, the most commonly used for high level expression o f foreign protein being the galactose-inducible promoters G A L l, GAL7, and GAL 10 (Romanos et al., 1992). These promoters can be rapidly switched on by the addition galactose to a growth medium lacking glucose (Johnson, 1987). Such strong and highly inducible promoters can enable high level expression o f proteins considered toxic to yeast, saturating the proteolytic systems as a result o f massive recombinant protein synthesis (Siest et al., 1993). As with the E. coli expression system, shuttle vectors have been designed to express the gene as a fusion protein, thereby aiding the purification procedure.
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G proteins modulate invertebrate synaptic calcium channel (LCav2) differently from the classical voltage dependent regulation of mammalian Cav2 1 and Cav2 2 channels

G proteins modulate invertebrate synaptic calcium channel (LCav2) differently from the classical voltage dependent regulation of mammalian Cav2 1 and Cav2 2 channels

accessory subunits: 21 (NP_037051), 1b (NP_059042)] and sometimes G-protein subunits G1 (AAD00650) and 2 (AAB82554) harbored in mammalian expression vectors were heterologously expressed by transfection using either calcium- phosphate or Lipofectamine (Invitrogen Canada, Burlington, Ontario) into human embryonic kidney cell line (HEK293T, M. Calos, Stanford University, USA) at 40–50% confluency. HEK- 293T cells were cultured in DMEM with 10% FBS and supplemented with 0.5% (v/v) penicillin–streptomycin solution. At least 3–4h before transfection, cells were re-plated in 60mm (diameter) sterile Petri dishes containing 3–6 pre-sterilized poly- lysine coated glass cover slips (Circles No. 1; 0.13–0.17mm thick; size, 12mm; Fisher Scientific Canada, Ottawa, Ontario) used for recording. After overnight transfection, the cells were washed twice with culture media and incubated at 28°C in a humidified, 5% CO 2
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The L type calcium channel in the heart: the beat goes on

The L type calcium channel in the heart: the beat goes on

(PP-1) removes phosphate at Ser16 in PLN and is upregulated in heart failure. Calstabin2 (FKB12.6) plays a role in stabilizing RyR2 in order to help maintain the channel in a closed state during diastole. RyR2 is hyperphosphorylated in heart failure, and calstabin2 dissociates from RyR2. Elevated NCX is an adaptive change in heart failure that becomes maladaptive and may be responsible for both arrhythmogenesis and contractile dysfunction. PKC-α expression and activity are elevated in heart failure. Calcineurin (CN) is activated by sustained elevation of [Ca 2+ ] i . It dephosphorylates nuclear factor of activated T cells (NFAT), enabling its translocation to the nucleus, which is sufficient to induce
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Analytical models of calcium binding in a calcium channel

Analytical models of calcium binding in a calcium channel

We make a final remark on how to use the simple alge- braic model (4)-(7) for real protein structures. This model has been applied to study the binding mechanism of one Ca 2+ and three Na + binding sites in the sodium/calcium exchanger (NCX) crystallized by Liao et al. in Ref. 32. Detailed analysis and results of modeling the NCX transporter will be reported elsewhere. Here, we outline our approach starting with the structure of NCX provided in the Protein Data Bank 91 (PDB ID: 3v5u) that contains 4591 atoms and four binding ions, namely, one Ca 2+ ion and three Na + ions (denoted by HET- ATM in the PDB file) for which the occupancy numbers rang- ing from 0.54 to 1 are given in the file.
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A Calcium Conducting Channel Akin to a Calcium Pump

A Calcium Conducting Channel Akin to a Calcium Pump

The chances of seeing the ryanodine sensitive Ca2 + release channel would be expected to be very low since the junctional membrane containing this channel is only 4.5% of the whole sarco[r]

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Analytical Models of Calcium Binding in a Calcium Channel

Analytical Models of Calcium Binding in a Calcium Channel

Here we show that important binding properties of the calcium channel can be calculated by algebra alone using the Fermi like distribution that takes into account ions of any size and water molecules and satisfies the saturation condition of ionic concentrations in mean field theory. In a certain sense, the Fermi distribution allows analysis much as classical statisti- cal mechanics allows analysis using the Boltzmann distribution. Neither needs differential equations or boundary conditions to describe many important (e.g., integral) properties of binding systems. Partial differential equations are needed to probe spatial profiles–and we use them here–and will be needed to explore time dependence and dissipation [6, 11, 29—31]. This paper is organized with an introduction to the all-spheres model and a general discussion of the Fermi approach to ions and water in solutions and channels in Section 2. The anomalous mole fraction effect and the Lipkind-Fozzard molecular model are presented in Section 2.1. Section 2.2 contains all algebraic formulas derived from the Fermi distribution and all numerical results of binding phenomena obtained directly from the experimental data and these formulas. The Poisson-Fermi differential equation [15, 25] is given Section 2.3 and then used to look into the channel with more resolution. The energy and concentration profiles are outputs of both algebraic Fermi and Poisson-Fermi differential equations. They are shown in Section 2.3, including the effects of a 10 6 -fold variation of the Ca 2+ bath
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Dominant-negative synthesis suppression of voltage-gated calcium channel Cav2.2 induced by truncated constructs

Dominant-negative synthesis suppression of voltage-gated calcium channel Cav2.2 induced by truncated constructs

brane? From the electrophysiological data, GFP-Dom I–II coex- pressed with Dom III–IV resulted in small but reproducible whole-cell calcium channel currents and produced single channels whose properties, apart from frequency of observation, were indistinguishable from wild type. Therefore, at least a small proportion of the truncated constructs must be able to fold and assemble together correctly with the normal topology. Similar results have recently been obtained for coexpression of two do- main constructs of Ca v 1.1 (Ahern et al., 2001).

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Small-molecule CaVα1⋅CaVβ antagonist suppresses neuronal voltage-gated calcium-channel trafficking

Small-molecule CaVα1⋅CaVβ antagonist suppresses neuronal voltage-gated calcium-channel trafficking

Pharmacokinetic Properties of Compound 14. Voltage-dependence of activation and steady-state inactivation experiments in HEK- Ca v 2.2 revealed that compound 14 appears to be more potent than 6 or 2. These observations suggest that 14 may be more efficacious in vivo than 6 and 2. Before testing 14 in nociceptive and neuropathic pain using in vivo assays, we sought to understand the pharmacokinetic properties of the compound in the mouse. For i.v. administration, 14 was formulated as a solution at a final dose of 1 mg/kg. Plasma concentrations at various time points were determined using the LC-MS/MS technique ( SI Appendix, Fig. S15 ). The elimination half-life of 14 was 0.29 h. The amount of time that the maximum concentration of the drug was present in plasma (Tmax) was 0.083 h, and the peak plasma concentration (Cmax) that Fig. 4. Compound 14 (BTT-369) reduces the current density and modulates the voltage-dependence of activation and steady-state inactivation of Ca V 2.2. (A) The Ca V 2.2 current densities in HEK-Ca V 2.2 cells pretreated for 48 h with DMSO (n = 15), 14 (n = 12), or 2 (n = 9). (Left) the superimposed raw sample traces of Ca V 2.2 currents acquired during the 20-ms depolarizing pulses in HEK-Ca V 2.2 cells pretreated with the indicated compounds for 48 h. (Right) Summary of the data. ***P < 0.001. (B) The concentration–effect curve for 14. HEK-Ca V 2.2 cells were pretreated with various concentrations of compound 14 for 48 h. Ca V 2.2 currents were acquired during 20-ms depolarizing pulses, and the current densities were calculated as a ratio of the peak current amplitude and each cell capacitance (0.1 μM, n = 6; 1 μM, n = 7; 10 μM, n = 8; 50 μM, n = 12). The line is the fit of the data to the four-parameter logistic function. The apparent IC 50 value is 31 μM. The same datasets for 50 μM 14 (BTT369) were used in A and B. (C) Effect of 2 (BTT-245) and 14 on the voltage dependence of the steady-state inactivation of Ca V 2.2 channels. The Inset shows two superimposed traces acquired during the steady-state inactivation protocol shown below the plot. HEK- Ca V 2.2 cells were pretreated with the indicated compounds for 48 h. *P < 0.05. (D) Effects of 2 and 14 on the voltage dependence of the activation of Ca V 2.2 channels in HEK-Ca V 2.2 cells pretreated with the vehicle or the indicated compounds for 48 h. (Left) The average current –voltage relationships ac- quired during voltage ramps for each test group. (Right) The average G –V curves for each treatment group. The gray vertical lines are error bars indicating SEM. (E) Acute effects of DMSO and 14 on the voltage dependence of the activation of Ca V 2.2 channels in HEK-Ca V 2.2 cells. (Left) Average G –V curves before and after 5-min incubation with DMSO (P > 0.05). (Right) Average G–V curves before and after 5-min incubation with 14 (P < 0.01). The gray vertical lines are error bars indicating SEM. ns, not significant.
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Demonstration of Binding of Neuronal Calcium Sensor-1 to the Ca(v)2.1 P/Q-Type Calcium Channel

Demonstration of Binding of Neuronal Calcium Sensor-1 to the Ca(v)2.1 P/Q-Type Calcium Channel

The precise details of the NCS-1 interaction are still to be elucidated. In rat primary neurons NCS-1 appears to play a role during CDF (20) and in Drosophila, loss of the NCS-1 orthologue Frequenin leads to reduced Ca 2+ entry into neurons and defective synaptic transmission (23). These data suggest that at least one function of NCS-1 is in positively regulating P/Q channel opening. Our data now provide an attractive biochemical explanation for these cellular studies and act as a platform for further cellular and structural investigations studying the interplay between CaM and NCS-1 during regulation of P/Q channel activity. CaM is expressed in all neurons and one possibility is that specific neuronal populations that also express NCS-1 are able to utilise this Ca 2+ -sensor as an additional modulator of P/Q activity. NCS-1 has a higher Ca 2+ affinity than CaM (15, 46) and therefore could potentially interact with the IQ motif over a different range of local Ca 2+ -concentrations to modulate activity independently of CaM. As Ca 2+ concentrations increase CaM could then displace NCS-1 to exert its documented roles in CDF and CDI. The N- and C-lobes of CaM, as described, exert distinct modes of P/Q-channel regulation. NCS-1, unlike CaM, does not have distinct lobes but rather a compact globular structure (47). The orientations of the N and C lobes with respect to one another differ in the two proteins, giving rise to different conformations of the ligand-binding site. Residues from both lobes in NCS-1 together form a large, contiguous solvent exposed hydrophobic ligand-binding crevice, resembling the palm of a partially-open hand. In Ca 2+ /CaM-PQIQ complex, the hydrophobic binding pocket is more enclosed, resembling a closed hand which envelopes the PQIQ peptide. It is, therefore, not possible to model a structure of NCS-1 in complex with the PQIQ peptide based on the Ca 2+ /CaM complex structure. It is likely that binding the PQIQ peptide would require a significant conformational change to the overall structure of NCS-1 in order to accommodate the peptide.
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Scanning mutagenesis of the I-II loop of the Cav2.2 calcium channel identifies residues Arginine 376 and Valine 416 as molecular determinants of voltage dependent G protein inhibition

Scanning mutagenesis of the I-II loop of the Cav2.2 calcium channel identifies residues Arginine 376 and Valine 416 as molecular determinants of voltage dependent G protein inhibition

are indicated beneath the corresponding columns (see METHODS for full description of the mutations used). Of the various conditions examined only the mutations R376A, R376F, V416A, and the double mutation R376A, V416A resulted in a significant loss of Gbg-mediated channel inhibition, as measured by the degree of pre-pulse relief following a depolarizing pre-pulse, when compared to WT control (*p < 0.05, t-test, **p < 0.05 one-way ANOVA, Dunnett ’ s method, or Kruskal-Wallis one-way ANOVA on ranks). Numbers in parentheses indicate numbers of cells tested for the respective condition. B : Histogram summarizing the results of PPF experiments using tsA-201 cells co-transfected to express a 1B mutant
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Deletion of a specific exon in the voltage gated calcium channel gene cacophony disrupts locomotion in Drosophila larvae

Deletion of a specific exon in the voltage gated calcium channel gene cacophony disrupts locomotion in Drosophila larvae

channel has been implicated in synaptogenesis, regulation of gene expression, and neurotransmission at the neuromuscular junction (Brosenitsch and Katz, 2001; Kawasaki et al., 2004). The C- terminus of the gene coordinates channel inactivation, modulation by G-proteins, modulation by calmodulin (CAM; as there is a CAM- binding site), and protein – protein interactions that regulate activity and/or target the channel to specific cellular compartments (Gray et al., 2007). Inclusion and exclusion of specific exons of the channel are tissue specific and confer functional specificity. For example, in mice, exon 37a is expressed preferentially in the dorsal root ganglia, where it functions to increase the sensitivity of the N-type channel to the voltage-independent form of G-protein modulation (Gray et al., 2007). Therefore, natural variants of Ca v 2.2
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The Voltage Sensor in Voltage-Dependent Ion Channels

The Voltage Sensor in Voltage-Dependent Ion Channels

The proportion of the maximum immobilizable charge to total charge was verified to also be two-thirds in the human skeletal muscle Na channel, and the time course of immobilization followed the time course of inactivation. The question then asked was which S4 was responsible for that immobilization. The logic of the ex- periments was to label each one of the four S4 segments, one at a time, with a fluorescent probe and look for changes in fluorescence that could be related to the set- tling and recovery from inactivation. The fluorescence kinetics followed the time course of activation and deac- tivation when the fluorophore was attached to the S4 segment of domain I or domain II (see Fig. 15, A–C) showing no component that had the time course of inac- tivation. Furthermore, a depolarizing prepulse that pro- duced inactivation had no effect on the fluorescence sig- nal during the test pulse, as if charge immobilization had no influence in the movements detected near the S4 of domains I and II. A different result was obtained in do- mains III and IV. In the case of domain III, a component of the fluorescent signal followed the time course of inacti- vation, superimposed on the activation time course. Also, deactivation of the fluorescence signal in domain III was preceded by a delay for pulses that developed inactiva- tion, and a prepulse experiment abolished a large fraction of the fluorescence signal. In domain IV, the effects were even more pronounced than in domain III, and the inac- tivation had a clear correlate with the fluorescence signal during activation. The deactivation kinetics time course also became slower as the inactivation during the pulse settled (see Fig. 15, D–F) and the prepulse experiment abolished the fluorescence signal completely. These re- sults indicate that charge immobilization is the result of S4 immobilization of domain III and IV but not I and II, giving the molecular basis for the nonimmobilizable com- ponent (domains I and II) and the immobilizable compo- nent (domains III and IV) of the gating charge. The in- volvement of domains III and IV has also been shown by mutagenesis and electrophysiological studies (26, 60, 89). During the operation of the Na channel, depolariza- tion moves all four S4 voltage sensors to their active position. The channel opens and the inactivating particle can now swing into position to inactivate the ionic cur- rent. After inactivation is settled, a repolarization allows the return to the resting position of the gating charge carried by the S4 segments of domains I and II, which is the nonimmobilizable component of the charge. The S4 segments of domain III and IV cannot go back until the inactivation particle dissociates from the domain; this
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<p>Anticancer Effects of Antihypertensive L-Type Calcium Channel Blockers on Chemoresistant Lung Cancer Cells via Autophagy and Apoptosis</p>

<p>Anticancer Effects of Antihypertensive L-Type Calcium Channel Blockers on Chemoresistant Lung Cancer Cells via Autophagy and Apoptosis</p>

Docetaxel (DOC) has anti-mitotic properties through the binding to microtubules (MTs) and preventing of depo- lymerization and stabilization of MTs. 4 Vincristine (VCR) is a classic anti-tubulin agent that induces disruption of MTs by binding to tubulin and inhibits tubulin polymer- ization/MT formation. 5 The action of VCR differs from that of DOC, which destabilizes MTs. Both DOC 6,7 and VCR 8,9 have been applied clinically as part of various cancer chemotherapy regimens. However, both drugs are a substrate of the ABCB1 transporter P-gp, so overexpres- sion of ABCB1 in cancer cells is considered the major phenotype of multidrug resistance to DOC and VCR. 10,11 There are many classes of antihypertensive, which lower blood pressure by different means. Among the most important and most widely used drugs are calcium channel blockers (CCBs), thiazide diuretics (TD), angio- tensin-converting enzyme inhibitors (ACEi), angiotensin II receptor antagonists (ARBs), and beta blockers (BBs). 12 L-type CCBs block the transmembrane fl ow of calcium, resulting in antagonism of vascular smooth muscle, con- traction of myocardial smooth muscle, reduction of blood pressure, and coronary artery dilation. 13,14 CCBs have assumed a major role in the treatment of patients with hypertension or coronary artery disease. CCBs can be broadly classi fi ed into 2 groups: dihydropyridine (DHP), such as Nifedipine (a 1,4-dihydropyridine, NIF); and non- dihydropyridine (non-DHP) groups. The prototypical agents of non-DHP group are Verapamil (a phenylalkyla- mine, VER), and Diltiazem (a benzothiazepinone, DIL). CCBs were the ninth most commonly prescribed class of drugs in the United States in 2009, with over 90 million prescriptions fi lled. 15
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Characterization of the molecular and electrophysiological properties of the T type calcium channel in human myometrium

Characterization of the molecular and electrophysiological properties of the T type calcium channel in human myometrium

Panel B HVA/LVA expressing cells mean± SE n=12 per point current density vs step voltage from a holding potential of -50mV closed circle and 80mV closed square.. Mean current density at [r]

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Expression of calcium channel transcripts in the zebrafish heart: dominance of T type channels

Expression of calcium channel transcripts in the zebrafish heart: dominance of T type channels

The wild-type Turku zebrafish line (kindly donated by Prof. Pertti Panula, University of Helsinki) was raised and maintained at the animal facilities of UEF (University of Eastern Finland, Joensuu) according to the established principles (Westerfield, 2007). The rearing temperature of the fish was 28°C. The experiments conform to the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Council of Europe No. 123, Strasbourg 1985) and were authorized by the national animal experimental board in Finland ( permission ESAVI/2832/04.10.07/2015).
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