Cx43 is involved in electrical remodeling of atrial myocytes through regu-lating L-type calcium current / 中国病理生理杂志

AIM:To investigate whether the association of connexin 43 ( Cx43 ) and L-type calcium channel involved in the pathogenesis of atrial fibrillation ( AF) .METHODS:The biochemical assays and whole-cell patch-clamp technique were used to study the expression of Cx43 in human atrial tissue.The co-localization of Cx43 and L-type calcium channel, and the regulation of L-type calcium current in atrial myocytes were investigated.RESULTS:The expression of Cx43 at mRNA and protein levels was decreased in human atrial tissues of AF patients.In cultured atrium-derived myocytes ( HL-1 cells) , knockdown of Cx43 significantly inhibited the mRNA expression of L-type calcium channelα1c subunit, as well as L-type calcium current.Co-localization of Cx43 with L-type calcium channel α1c subunit in mouse atrial myocytes was observed.CONCLUSION:The decrease in Cx43 is involved in the pathogenesis of AF, probably through reducing the L-type calcium current in atrial myoctyes by co-localization with L-type calcium channel, thus representing the potential pathogenesis in atrial fibrillation.

Effect of Simvastatin on ATP-sensitive K+ channels and L-type Ca2+ channels in mouse pancreatic beta cells / 中华老年医学杂志

Objective To observe the influence of Simvastatin on the ATP-sensitive K+Channels and L-type Ca2+ Channels in mouse pancreatic beta cell line MIN6.Methods MIN6 cells were divided into 0.05 ％ dimethyl sulfoxide (DMSO) group,normal control group and low-,middle-,high-concentration of Simvastatin treatment groups,that were cultured for 48 h with high-glucose DMEM containing 15％ fetal bovine serum plus 0.05％ dimethyl sulfoxide,0,2,5 and 10 μmol/Lsimvastatin,respectively.Whole-cell patch-clamp technology was used to record the currents of ATP-sensitive K+ channels and L-type Ca2+ channels in MIN6 cells.Results The mean potassium current density in normal external solution perfusion group was (92.81 ±4.10) pA/pF.Compared with normal external solution perfusion control group,2,5 and 10 μmol/L Simvastatin treatments markedly enhanced the current density of ATP-sensitive K+ Channels,reaching to (117.94 ± 3.67)pA/pF,(153.91±12.38) pA/pF,(307.01±6.40) pA/pF (all P＜0.01),respectively.The current density in L-type Ca2+ Channels was (-21.03 ± 0.55) pA/pF in glucose external solution group.Compared with glucose external solution group,the current density in 2,5 and 10 μmol/L Simvastatin treatment groups were decreased to (16.31±0.51) pA/pF,(-10.75±0.71) pA/pF,(-3.30±0.46) pA/pF (all P＜0.01),respectively.Conclusions Simvastatin inhibits insulin secretion and glycometabolism in mouse pancreatic beta cell line MIN6 via enhancing the current density of ATP-sensitive K+ Channels and inhibiting the current density of L-type Ca2+ Channels.

Antischistosomal activity of a calcium channel antagonist on schistosomula and adult Schistosoma mansoni worms

Current schistosomiasis control strategies are largely based on chemotherapeutic agents and a limited number of drugs are available today. Praziquantel (PZQ) is the only drug currently used in schistosomiasis control programs. Unfortunately, this drug shows poor efficacy in patients during the earliest infection phases. The effects of PZQ appear to operate on the voltage-operated Ca2+channels, which are located on the external Schistosoma mansoni membrane. Because some Ca2+channels have dihydropyridine drug class (a class that includes nifedipine) sensitivity, an in vitro analysis using a calcium channel antagonist (clinically used for cardiovascular hypertension) was performed to determine the antischistosomal effects of nifedipine on schistosomula and adult worm cultures. Nifedipine demonstrated antischistosomal activity against schistosomula and significantly reduced viability at all of the concentrations used alone or in combination with PZQ. In contrast, PZQ did not show significant efficacy when used alone. Adult worms were also affected by nifedipine after a 24 h incubation and exhibited impaired motility, several lesions on the tegument and intense contractility. These data support the idea of Ca2+channels subunits as drug targets and favour alternative therapeutic schemes when drug resistance has been reported. In this paper, strong arguments encouraging drug research are presented, with a focus on exploring schistosomal Ca2+channels.

Vasorelaxant effects of calcium channel blockers on isolated thoracic aortic rings from thyroxine-induced hypertensive rats / 中国药理学通报

Aim To investigate the effects of T-and L-type calcium channel blockers on isolated thoracic aorta from thyroxine-induced hypertensive rats.Methods Hyperthyroidism was induced by administering L-thyroxine (T4,0.5 mg·kg~(-1),sc) daily for 16 days.Sham-treated euthyroid control rats were only received vehicle saline for 16 days. Experiments were performed in isolated thoracic aorta rings from euthyroid and hyperthyroid rats. Mibefradil and diltiazem were used to inhibit T-and L-type calcium channels,respectively.Results Thyroid hormone excess for 16 days induced characteristic changes in body weight,heart rate and systolic blood pressure in rats. The body weight was significantly decreased,heart rate and systolic blood pressure were increased in T4-treated rats. Thoracic aorta morphology was altered in T4-treated rats. The thickness of adventitia was increased with hypertrophy and hyperplasia of the smooth musle cells in T4-treated rats. Vasorelaxant effect of T-and L-type calcium channel blockers were accentuated in aortic rings from T4-treated rats.Conclusion These data suggest that T-and L-type calcium channels are functionally upregulated in isolated thoracic aorta from hyperthyroid rats and they,may be a therapeutic target in thyroxine-induced hypertension.

Nitric Oxide Synthase Mediates Carbon Monoxide-Induced Stimulation of L-type Calcium Currents in Human Jejunal Smooth Muscle Cells

Exogenous carbon monoxide (0.2%) increases L-type calcium (Ca2+) current in human jejunal circular smooth muscle cells. The stimulatory effect of carbon monoxide (CO) on L-type Ca2+ current is inhibited by pre-application of L-NNA, a classical competitive inhibitor of nitric oxide synthase (NOS) with no significant isoform selectivity (Lim, 2003). In the present study, we investigated which isoform of NOS affected CO induced stimulation of L-type Ca2+ current in human jejunal circular smooth muscle cells. Cells were voltage clamped by whole-cell mode patch clamp technique, and membrane currents were recorded with 10 mM barium as the charge carrier. Before the addition of CO, cells were pretreated with each inhibitor of three NOS isoforms for 15 minutes. CO-stimulating effect on L-type Ca2+ current was partially blocked by N- (3- (Amino-methyl) benzyl) acetamidine-2HCl (1400W, an iNOS inhibitor). On the other hand, 3-bromo-7-nitroindazole (BNI, a nNOS inhibitor) or N5- (1-Iminoethyl)-L-ornithine dihydrochloride (L-NIO, an eNOS inhibitor) completely blocked the CO effect. These data suggest that low dose of exogenous CO may stimulate all NOS isoforms to increase L-type Ca2+ channel through nitric oxide (NO) pathway in human jejunal circular smooth muscle cells.

The Effect of Carbon Monoxide on L-type Calcium Channel Currents in Human Intestinal Smooth Muscle Cells

Carbon monoxide (CO) is low molecular weight oxide gas that is endogenously produced under physiological conditions and interacts with another gas, nitric oxide (NO), to act as a gastrointestinal messenger. The aim of this study was to determine the effects of exogenous CO on L-type calcium channel currents of human jejunal circular smooth muscle cells. Cells were voltage clamped with 10 mM barium (Ba2+) as the charge carrier, and CO was directly applied into the bath to avoid perfusion induced effects on the recorded currents. 0.2% CO was increased barium current (I (Ba) ) by 15+/-2% (mean+/-S.E., p 0.05). CO mediates inhibitory neurotransmission through the nitric oxide pathway. Therefore, to determine if the effects of CO on L-calcium channels were also mediated through NO, cells were incubated with N (G) -nitro-L-arginine (L-NNA, 1 mM), a nitric oxide synthase inhibitor. After L-NNA pretreatment, 0.2 % CO did not increase barium current (4+/-2% increase, n=6, p> 0.05). NO donor, SNAP (20 microM) increased barium current by 13+/-2% (n=6, p< 0.05) in human jejunal smooth muscle cells. These data suggest that CO activates L-type calcium channels through NO/cGMP dependant mechanism.

Effect of quaternary ammonium salt derivative of haloperidol on L-type currents in rat ventricular myocytes / 中国药理学通报

AIM To study the effect of quaternary ammonium salt derivative of haloperidol (F 2) on L type calcium current ( I Ca ) in rat ventricular myocytes. METHODS Single ventricular cell of rat was obtained by enzymatic dissociation method. The currents were recorded with the whole cell configuration of the patch clamp technique. RESULTS F 2(1 ?mol?L -1 ) decreased I Ca from ( 1 775 2 ?360 4) pA to (464?129 1) pA ( n =8, P

Influence of Sodium Nitroprusside on Cell Motility of Outer Hair Cells of Guinea Pigs / 听力学及言语疾病杂志

Objective To study the changes of cell motility of outer hair cells in the cochlear of guinea pigs under treatment of sodium nitroprusside(SNP). Methods By using the whole cell patch clamp recording technique in normal external and internal cell solution, the cell motility of outer hair cells under stimulation of voltage was observed in different concentration of SNP. Results Sodium nitroprusside apparently inhibited outer hair cells' motility when SNP concentration was higher than 100 ?Mol/L ( P