Calcium currents, inhibition

Junge HJ, Rhee JS, Jahn O et al (2004) Calmodulin and Muncl3 form a Ca2+ sensor/effector complex that controls short-term synaptic plasticity. Cell. 118 389 401 Kajikawa Y, Saitoh N, Takahashi T (2001) GTP-binding protein beta gamma subunits mediate presynaptic calcium current inhibition by GABA(B) receptor. Proc Natl Acad Sci USA... 

Inhibition of calcium currents Inhibition of adenylate cyclase Elevation of intracellular calcium... 

Mackie K, Devane WA, Hille B. Anandamide, an endogenous cannabinoid, inhibits calcium currents as a partial agonist in N-18 neuroblastoma cells. Mol Pharmacol 1993 44 498-503. 

Taussig R, Sanchez S, Rifo M, Gilman AG, Delardetti F. Inhibition of the omega conotoxin-sensitive calcium current by distinct G proteins. Neuron 1992 8 799-809. 

A benzopyran derivative, RP-58866 (70) is under development by Rhone-Poulenc. Patch clamp studies in guinea-pig ventricular myocytes indicate that RP-58866 inhibits the inward rectifying potassium current (7ki) with no effects on the delayed rectifier, ATP-sensitive potassium currents or calcium currents [200]. RP-58866 increases APD90 of Purkinje fibres by about 45% at 0.3 yuM without affecting K ax [201]. The compound was effective... 

IV Ibutilide Dofetilide Verapamil Diltiazem BepridiP Inhibit the slow inward calcium current, minimal effect (decrease) on ventricular action potential, major effects on the atrioventricular node to slow conduction velocity and increase the ERP. 

Type II Multiple actions enhance GABAergic inhibition, reduce T-calcium currents, and possibly block SRF Valproic acid Benzodiazepines Phenobarbital Primidone... 

Noncategorized Has no known effect on SRF, GABAergic inhibition, or T-calcium currents Gabapentin ... 

Cheng B, McMahon DG, Mattson MP Modulation of calcium current, intracellular calcium levels and cell survival by glucose deprivation and growth factors in hippocampal neurons. Brain Res 607 275-285, 1993 Cheng CHK, Costall B, Kelly ME, et al Actions of 5-hydroxytryptophan to inhibit and disinhibit mouse behaviour in the hght dark test. Eur J Pharmacol 255 39-49, 1994... 

Adenosine is a nucleoside that occurs naturally throughout the body. Its half-life in the blood is less than 10 seconds. Its mechanism of action involves activation of an inward rectifier K+ current and inhibition of calcium current. The results of these actions are marked hyperpolarization and suppression of calcium-dependent action potentials. When given as a bolus dose, adenosine directly inhibits atrioventricular nodal conduction and increases the atrioventricular nodal refractory period but has lesser effects on the sinoatrial node. Adenosine is currently the drug of choice for prompt conversion of paroxysmal supraventricular tachycardia to sinus rhythm because of its high efficacy (90-95%) and very short duration of action. It is usually given in a bolus dose of 6 mg followed, if necessary, by a dose of 12 mg. An uncommon variant of ventricular tachycardia is adenosine-sensitive. The drug is less effective in the presence of adenosine receptor blockers such as theophylline or caffeine, and its effects are potentiated by adenosine uptake inhibitors such as dipyridamole. 

Ethosuximide has an important effect on Ca2+ currents, reducing the low-threshold (T-type) current. This effect is seen at therapeutically relevant concentrations in thalamic neurons. The T-type calcium currents are thought to provide a pacemaker current in thalamic neurons responsible for generating the rhythmic cortical discharge of an absence attack. Inhibition of this current could therefore account for the specific therapeutic action of ethosuximide. 

These compounds are active against pentylenetetrazol-induced seizures. Trimethadione raises the threshold for seizure discharges after repetitive thalamic stimulation. It—or, more notably, its active metabolite dimethadione—has the same effect on thalamic Ca2+ currents as ethosuximide (reducing the T-type calcium current). Thus, suppression of absence seizures is likely to depend on inhibiting the pacemaker action of thalamic neurons. 

Parekh, A. B., 1998, Slow feedback inhibition of calcium release-activated calcium current by calcium entry. J Biol Chem 273, 14925—32. 

Hopf, F.W., Reddy, P., Hong, J., and Steinhardt, R.A., 1996a, A capacitative calcium current in cultured skeletal muscle cells is mediated by the calcium-specific leak channel and inhibited by dihydropyridine compounds, J Biol Chem, 271, pp 22358-22367. 

PC12) cells. Inhibition of L-type Ca2+ currents by phenothiazine drug was also found in invertebrate neurons. Investigations performed by Cruzblanca et al. [266] revealed that TFP (5) caused reversible and dose-dependent reduction of L-type Ca2+ currents in Helix aspersa (brown snail) neurons. The efficacy of inactivation of this current was enhanced by this drug. The possibility that calcium currents were altered by the influence of TFP (5) on the protein kinase C (PKC) activity was excluded in this paper. 

Apart from HCN channels, genistein (42) also acted on other types of channels present in cardiac cells. Chiang et al. [306] examined the impact of this isoflavone on the L-type calcium and cAMP- dependent chloride currents in guinea pig ventricular myocytes. Using the voltage-clamp technique they found that genistein (42) reversibly inhibited L-type calcium currents in a dose-dependent manner. Surprisingly daidzein (40), which was ineffective with respect to many other channel types, also decreased L-type calcium currents in myocytes. Opposite to calcium currents, the cAMP-dependent... 

Unlike genistein (42), quercetin (29) [308,309] and myricetin (31) [310] enhanced the calcium current carried by L-type calcium channels of the myocytes from rat tail artery. The character of voltage-, concentration-, and frequency-dependent calcium current changes induced by myricetin (31) [310] allowed the conclusion that this flavonoid exerted its effect on L-type calcium channels by binding preferentially to the channels in the inactivated state. Quercetin stimulated L-type calcium channels in rat pituitary GH3 cells in a dose-dependent manner [309]. The EC50 value was about 7 xM, and many facts suggested direct interaction between ion channels and flavonoid. In NG 108-15 neuronal cells quercetin (29) caused inhibition of TTX-sensitive sodium current. 

Bean BP (1989) Neurotransmitter inhibition of neuronal calcium currents by changes in channel voltage dependence. Nature 340 153-6... 

Caulfield MP, Jones S, Vallis Y, Buckley NJ, Kim GD, Milligan G, Brown DA (1994) Muscarinic M-current inhibition via G alpha q/11 and alpha-adrenoceptor inhibition of Ca2+ current via G alpha o in rat sympathetic neurones. J Physiol 477 Pt 3 415-22 Charvin N, L Eveque C, Walker D, Berton F, Raymond C, KataokaM, Shoji-Kasai Y, Takahashi M, De Waard M, Seagar MJ (1997) Direct interaction of the calcium sensor protein synaptotagmin I with a cytoplasmic domain of the alphal A subunit of the P/Q-type calcium channel. Embo J 16 4591-6... 

Cribbs LL, Lee JH, Yang J, Satin J, Zhang Y, Daud A, Barclay J, Williamson MP, Fox M, Rees M, Perez-Reyes E (1998) Cloning and characterization of alphalH from human heart, a member of the T-type Ca2+ channel gene family. Circ Res 83 103-9 Currie KP, Fox AP (1997) Comparison of N- and P/Q-type voltage-gated calcium channel current inhibition. J Neurosci 17 4570-9... 

Golard A, Siegelbaum SA (1993) Kinetic basis for the voltage-dependent inhibition of N-type calcium current by somatostatin and norepinephrine in chick sympathetic neurons. J Neurosci 13 3884-94... 

Delmas P, Abogadie FC, Dayrell M et al (1998a) G-proteins and G-protein subunits mediating cholinergic inhibition of N-type calcium currents in sympathetic neurons. Eur J Neurosci 10 1654-66... 

Ehrlich I, Elmslie KS (1995) Neurotransmitters acting via different G proteins inhibit N-type calcium current by an identical mechanism in rat sympathetic neurons. J Neurophysiol 74 2251-7 Esser L, Wang CR, Hosaka M et al (1998) Synapsin I is structurally similar to ATP-utilizing enzymes. EMBO J 17 977-84... 

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