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Voltage-dependent Manner (voltage-dependent + manner)

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Medical Sciences	100%

Selected Abstracts

Electrophysiological and Neurochemical Evidence for Voltage-Dependent Ca2+ Channel Blockade by a Novel Neuroprotective Agent NS-7,

BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2001
Michiko Oka
In rat dorsal root ganglion neurones, NS-7 (0.3,100 ,M) inhibited the whole-cell Ba2+ currents (IBa) in a voltage-dependent manner, in which the compound more potently blocked the IBa elicited from the holding potential of ,40 mV than that induced from ,80 mV. In slices of rat cerebral cortex, KCl-evoked nitric oxide synthesis was markedly inhibited by ,-conotoxin GVIA and ,-agatoxin IVA, but only slightly attenuated by nifedipine, suggesting that the response is mediated predominantly through activation of N-type and P/Q-type Ca2+ channels. NS-7 (1,100 ,M) inhibited the KCl-stimulated nitric oxide synthesis in a manner dependent on the intensity of the depolarizing stimuli. Moreover, weak but significant inhibitory effect of NS-7 was observed even after wash-out. Similar voltage-dependent inhibition of the KCl response was observed by a limited concentration (10 ,M) of verapamil. These findings indicate that NS-7 in several concentrations blocks Ca2+ channel in a voltage-dependent manner. [source]

The actions of azelnidipine, a dihydropyridine-derivative Ca antagonist, on voltage-dependent Ba2+ currents in guinea-pig vascular smooth muscle

BRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2006
H-L Zhu
Background and purpose: Although azelnidipine is used clinically to treat hypertension its effects on its target cells, Ca2+ channels, in smooth muscle have not been elucidated. Therefore, its effects on spontaneous contractions and voltage-dependent L-type Ca2+ channels were investigated in guinea-pig portal vein. Experimental approach: The inhibitory potency of azelnidipine on spontaneous contractions in guinea-pig portal vein was compared with those of other dihydropyridine (DHP)-derived Ca antagonists (amlodipine and nifedipine) by recording tension. Also its effects on voltage-dependent nifedipine-sensitive inward Ba2+ currents (IBa) in smooth muscle cells dispersed from guinea-pig portal vein were investigated by use of a conventional whole-cell patch-clamp technique. Key results: Spontaneous contractions in guinea-pig portal vein were reduced by all of the Ca antagonists (azelnidipine, Ki=153 nM; amlodipine, Ki=16 nM; nifedipine, Ki=7 nM). In the whole-cell experiments, azelnidipine inhibited the peak amplitude of IBa in a concentration- and voltage-dependent manner (-60 mV, Ki=282 nM; ,90 mV, Ki=2 ,M) and shifted the steady-state inactivation curve of IBa to the left at ,90 mV by 16 mV. The inhibitory effects of azelnidipine on IBa persisted after 7 min washout at ,60 mV. In contrast, IBa gradually recovered after being inhibited by amlodipine, but did not return to control levels. Both azelnidipine and amlodipine caused a resting block of IBa at -90 mV. Only nifedipine appeared to interact competitively with S(-)-Bay K 8644. Conclusions and implications: These results suggest that azelnidipine induces long-lasting vascular relaxation by inhibiting voltage-dependent L-type Ca2+ channels in vascular smooth muscle. British Journal of Pharmacology (2006) 149, 786,796. doi:10.1038/sj.bjp.0706919 [source]

Quercetin as a novel activator of L-type Ca2+ channels in rat tail artery smooth muscle cells

BRITISH JOURNAL OF PHARMACOLOGY, Issue 7 2002
Simona Saponara
The aim of this study was to investigate the effects of quercetin, a natural polyphenolic flavonoid, on voltage-dependent Ca2+ channels of smooth muscle cells freshly isolated from the rat tail artery, using either the conventional or the amphotericin B-perforated whole-cell patch-clamp method. Quercetin increased L-type Ca2+ current [ICa(L)] in a concentration- (pEC50=5.09±0.05) and voltage-dependent manner and shifted the maximum of the current-voltage relationship by 10 mV in the hyperpolarizing direction, without, however, modifying the threshold and the equilibrium potential for Ca2+. Quercetin-induced ICa(L) stimulation was reversible upon wash-out. T-type Ca2+ current was not affected by quercetin. Quercetin shifted the voltage dependence of the steady-state inactivation and activation curves to more negative potentials by about 5.5 and 7.5 mV respectively, in the mid-potential of the curves as well as increasing the slope of activation. Quercetin slowed both the activation and the deactivation kinetics of the ICa(L). The inactivation time course was also slowed but only at voltages higher than 10 mV. Moreover quercetin slowed the rate of recovery from inactivation. These results prove quercetin to be a naturally-occurring L-type Ca2+ channel activator. British Journal of Pharmacology (2002) 135, 1819,1827; doi:10.1038/sj.bjp.0704631 [source]

Voltage-dependent inhibition of the muscarinic cationic current in guinea-pig ileal cells by SK&F 96365

BRITISH JOURNAL OF PHARMACOLOGY, Issue 4 2000
A V Zholos
The effects of SK&F 96365 on cationic current evoked either by activating muscarinic receptors with carbachol or by intracellularly applied GTP,S (in the absence of carbachol) were studied using patch-clamp recording techniques in single guinea-pig ileal smooth muscle cells. SK&F 96365 reversibly inhibited the muscarinic receptor cationic current in a concentration-, time- and voltage-dependent manner producing concomitant alteration of the steady-state I-V relationship shape which could be explained by assuming that increasing membrane positivity increased the affinity of the blocker. The inhibition was similar for both carbachol- and GTP,S-evoked currents suggesting that the cationic channel rather than the muscarinic receptor was the primary site of the SK&F 96365 action. Increased membrane positivity induced additional rapid inhibition of the cationic current by SK&F 96365 which was more slowly relieved during membrane repolarization. Both the inhibition and disinhibition time course could be well fitted by a single exponential function with the time constants decreasing with increasing positivity for the inhibition (e -fold per about 12 mV) and approximately linearly decreasing with increasing negativity for the disinhibition. At a constant SK&F 96365 concentration, the degree of cationic current inhibition was a sigmoidal function of the membrane potential with a potential of half-maximal increase positive to about +30 mV and a slope factor of about ,13 mV. Increasing the duration of voltage steps at ,80 or at 80 mV, increased the percentage inhibition; the degree of inhibition was almost identical at both potentials providing evidence that the same cationic channel was responsible for the cationic current both at negative and at positive potentials. It is concluded that the distinctive and unique mode of SK&F 96365 action on the muscarinic receptor cationic channel is a valuable tool in future molecular biology studies of this channel. British Journal of Pharmacology (2000) 129, 695,702; doi:10.1038/sj.bjp.0703115 [source]