asopressin is one of the physiologically active peptides that regulate humoral immunity by promoting reabsorption of water in the kidney and simultaneously having a potent vasoconstrictive action on vascular smooth muscle by increasing the production of inositol 1,4,5-triphosphate (IP3) and 1,2-diacylglycerol (DG) and activating the voltage-dependent Ca channel, which results in elevation of the intracellular Ca concentration. 1,2 Recently, it has been reported that secretion of vasopressin increases in pathophysiological conditions such as angina pectoris, acute myocardial infarction and chronic heart failure. 3 During such conditions of metabolic inhibition, activation of the sarcolemmal KATP channel 4 is known to regulate Ca 2+ entry and myocardial contractility in order to lessen the myocardial damage. 5,6 Moreover, activation of this channel minimizes the infarct area in animal models 7 and elicits a cardioprotective action in dogs with pacinginduced heart failure. 8 On the other hand, its activation has been reported to shorten the action potential duration, thereby in part acting arrhythmogenically in acute ischemia. 9,10 Moreover, Martin et al 2 reported that vasopressin inhibited the sarcolemmal KATP channels and activated the voltage-dependent Ca channel, thereby regulating insulin secretion in rat pancreatic -cells. Wakatsuki et al 11 reported that vasopressin activated Ca-activated K channels and simultaneously controlled vascular tone by suppressing sarcolemmal KATP channels in porcine coronary vascular smooth muscle cells in the cell-attached configuration. More recently, it has been reported that the vasopressin V1 Circulation Journal Vol.66, March 2002receptor couples to protein kinase C via activation of phospholipase C and that vasopressin V2 receptor links to G protein coupled protein kinase including adenylate cyclase. [12][13][14][15] In the central nervous system, Easaw 16 showed that vasopressin-inhibited the voltage-dependent outward current via the V1 receptor, and it activated the same current via the V2 receptor.Therefore vasopressin regulates excitation of neurons in a diagonal band of the rat. However, the action of vasopressin in the heart still remains controversial. The present study aimed to examine the physiological implication of vasopressin's effects on sarcolemmal KATP channel in enzymatically isolated guinea pig ventricular myocytes using both cell-attached and inside-out configurations. Methods Preparation of Single Ventricular CardiomyocytesAdult male guinea pigs of 250-300 g were anesthetized with pentobarbital sodium (40-50 mg/kg ip) and isolated ventricular cells were obtained using the collagenase perfusion method. 17 In brief, the chest was briefly opened under artificial ventilation, the aorta cannulated and the heart quickly dissected. Using a Langendorff apparatus, the heart was retrogradedly perfused with normal Tyrode's solution for about 5 min to wash out the blood in the vessels, followed by nominally Ca 2+ -free Tyrode's solution for about 3 min at 36°C. The h...