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Ba2+ Currents (ba2+ + current)
Selected Abstracts,-Conotoxin CVIB differentially inhibits native and recombinant N- and P/Q-type calcium channelsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2007Leonid Motin Abstract ,-Conotoxins are routinely used as selective inhibitors of different classes of voltage-gated calcium channels (VGCCs) in excitable cells. In the present study, we examined the potent N-type VGCC antagonist ,-conotoxin CVID and non-selective N- and P/Q-type antagonist CVIB for their ability to block native VGCCs in rat dorsal root ganglion (DRG) neurons and recombinant VGCCs expressed in Xenopus oocytes. ,-Conotoxins CVID and CVIB inhibited depolarization-activated whole-cell VGCC currents in DRG neurons with pIC50 values of 8.12 ± 0.05 and 7.64 ± 0.08, respectively. Inhibition of Ba2+ currents in DRG neurons by CVID (, 66% of total) appeared to be irreversible for >,30 min washout, whereas Ba2+ currents exhibited rapid recovery from block by CVIB (, 80% within 3 min). The recoverable component of the Ba2+ current inhibited by CVIB was mediated by the N-type VGCC, whereas the irreversibly blocked current (, 22% of total) was attributable to P/Q-type VGCCs. ,-Conotoxin CVIB reversibly inhibited Ba2+ currents mediated by N- (CaV2.2) and P/Q- (CaV2.1), but not R- (CaV2.3) type VGCCs expressed in Xenopus oocytes. The ,2,1 auxiliary subunit co-expressed with CaV2.2 and CaV2.1 reduced the sensitivity of VGCCs to CVIB but had no effect on reversibility of block. Determination of the NMR structure of CVIB identified structural differences to CVID that may underlie differences in selectivity of these closely related conotoxins. ,-Conotoxins CVIB and CVID may be useful as antagonists of N- and P/Q-type VGCCs, particularly in sensory neurons involved in processing primary nociceptive information. [source] Dihydropyridine- and voltage-sensitive Ca2+ entry in human parathyroid cellsEXPERIMENTAL PHYSIOLOGY, Issue 7 2009Keitaro Yokoyama Patch-clamp and fluorescence measurements of cytoplasmic Ca2+ concentration ([Ca2+]i) were performed to directly detect extracellular Ca2+ entry into cultured parathyroid cells from patients with secondary hyperparathyroidism. Cells loaded with fluo-3 AM or fluo-4 AM showed a transient increase in fluorescence (Ca2+ transient) following 10 s exposure to 150 mm K+ solution in the presence of millimolar concentrations of external Ca2+. The Ca2+ transient was completely inactivated after 30,40 s exposure to the high-K+ solution, was reduced by dihydropyridine antagonists and was enhanced by FPL-64176, an L-type Ca2+ channel agonist. The electrophysiological and pharmacological properties of the whole-cell Ca2+ and Ba2+ currents were similar to those of L-type Ca2+ channels. The Ca2+ transients induced by 10 s exposure to 3.0 mm extracellular Ca2+ concentration ([Ca2+]o) were inhibited by dihydropyridine antagonists and were partly inactivated following 30,40 s exposure to the high-K+ solution. These results demonstrate, for the first time, that human parathyroid cells express L-type-like Ca2+ channels that are possibly involved in the [Ca2+]o -induced change in [Ca2+]i. This Ca2+ entry system might provide a compensatory pathway for the negative feedback regulation of parathyroid hormone secretion, especially in hyperplastic conditions in which the Ca2+ -sensing receptor is poorly expressed. [source] Electrophysiological and Neurochemical Evidence for Voltage-Dependent Ca2+ Channel Blockade by a Novel Neuroprotective Agent NS-7,BASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2001Michiko 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] Acute exposure to low-level CW and GSM-modulated 900 MHz radiofrequency does not affect Ba2+ currents through voltage-gated calcium channels in rat cortical neuronsBIOELECTROMAGNETICS, Issue 8 2007Daniela Platano Abstract We have studied the non-thermal effects of radiofrequency (RF) electromagnetic fields (EMFs) on Ba2+ currents () through voltage-gated calcium channels (VGCC), recorded in primary cultures of rat cortical neurons using the patch-clamp technique. To assess whether low-level acute RF field exposure could modify the amplitude and/or the voltage-dependence of , Petri dishes containing cultured neurons were exposed for 1,3 periods of 90 s to 900 MHz RF-EMF continuous wave (CW) or amplitude-modulated according to global system mobile communication standard (GSM) during whole-cell recording. The specific absorption rates (SARs) were 2 W/kg for CW and 2 W/kg (time average value) for GSM-modulated signals, respectively. The results obtained indicate that single or multiple acute exposures to either CW or GSM-modulated 900 MHz RF-EMFs do not significantly alter the current amplitude or the current,voltage relationship of , through VGCC. Bioelectromagnetics 28:599,607, 2007. © 2007 Wiley-Liss, Inc. [source] The actions of azelnidipine, a dihydropyridine-derivative Ca antagonist, on voltage-dependent Ba2+ currents in guinea-pig vascular smooth muscleBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2006H-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] | |||||||||||||