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Carbachol exhibited positive inotropic effect on rat ventricular myocytes via M_(2) muscarinic receptors

Cui Xiangli, Chen Huanzhen, Wu Bowei

Department of physiology, Shanxi Medical University.Taiyuan 030001,Shanxi；Department of Physiology, Shanxi Medical University.Taiyuan 030001,Shanxi；China

Abstract

The present study was aimed to investigate the positive inotropic mechanism of carbachol (CCh) on rat ventricular myocytes. The effects of CCh on L-type calcium current (I_(Ca,L)) and Na~(+)/Ca~(2+) exchange current (I_(Na/Ca)) were investigated in isolated rat ventricular myocytes. After loading myocytes with Fura-2/AM, electrically triggered Ca~(2+) transient and cell shortening in single myocyte were measured simultaneously using ion imaging system with charge-coupled device (CCD) camera. CCh (100 #mu#mol/L)increased I_(Na/Ca) in forward mode from (1.18±0.57) pA/pF in the conrol group to (1.65±0.52) pA/pF (P＜0.01) and that in reverse mode from (1.11±0.49) pA/pF in the control group to (1.53±0.52) pA/pF (P＜0.01), respectively. CCh had no effect on I_(Ca,L). The stimulatory effect of CCh on I_(Na/Ca) was blocked by application of atropine, a non-selective M muscarinic receptor antagonist, and methoctramine,a selective M_(2) muscarinic receptor antagonist. CCh (100 #mu#mol/L) increased cell shortening from (3.00±0.67) #mu#m in the control group to (3.55±1.21) #mu#m. Ca~(2+) transient was also increased from 203.8±50.0 in the control group to 234.8±64.3 in 100 #mu#mol/L CCh group. KB-R7943, a selective inhibitor of reverse mode Na~(+)/Ca~(2+) exchange, did not change the baseline level of cell shortening and Ca~(2+) transient,while completely abolished CCh-induced increments of both Ca~(2+) transient and cell shortening. CCh increased cell shortening and Ca~(2+) transient in the presence of nicardipine, indicating that the positive inotropic effect of CCh was through activation of Na~(+)/Ca~(2+) exchange.Calcium sensitivity was not changed by CCh. Both atropine and methoctramine abolished the positive inotropic effects of CCh,demonstrating that CCh induced positive inotropism via the M_(2) muscarinic receptor. The results suggest that CCh increases cell contraction and Ca~(2+) transient in rat ventricular myocytes. This positive inotropic effect of CCh is through activation of reverse mode Na~(+)/Ca~(2+) exchange, and M_(2) receptors are involved in mediating CCh-induced contraction.

Key words: carbachol;muscarinic acetylcholine receptor;Na/Ca exchange;Calcium;methoctramine;Rat;Fura-2;imaging;Myocardium

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Citing This Article：

Cui Xiangli, Chen Huanzhen, Wu Bowei. Carbachol exhibited positive inotropic effect on rat ventricular myocytes via M_(2) muscarinic receptors. Acta Physiol Sin 2007; 59 (5): 667-673 (in Chinese with English abstract).