|Budget Amount *help
¥1,800,000 (Direct Cost : ¥1,800,000)
Fiscal Year 1997 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1996 : ¥900,000 (Direct Cost : ¥900,000)
Under ischemia, adenosine is produced by enzymatic dephosphorylation of adenosine 5'-monophosphate (5'-AMP) by 5'-nucleotidase. We studied the effect of potassium ions on the production of adenosine, using flexibly mounted microdialysi techniques. The microdialysisi probe was implanted into the left ventricular myocardium of anesthetized open-chested rats, followed by a perfusion with Tyrode solution containing 5'-AMP.We clarified that the level of dialysate adenosine measured during continued supply of 5'-AMP reflects the activity of endogenous ecto-5'-nucleotidase. When the concentration of KCI in the Tyrode solution was increased stepwise from 5.4 mM (control) to up to 140 mM,the level of dialysate adenosine significantly increased, in a concentration-dependent manner and the latter effect was abolished in the presence of 1 mM CsCI,aK^+ channel inhibitor. Equivalent increases in osmotic concentration of the Tyrode solution, made by adding sucrose (270 mM) , did not affect the dialys
ate adenosine concentration. In isolated guinea pig ventricular papillary muscles, the blockers of inward rectifier K^+ current (I_<K1>), i.e., CsCI and BaCI_2 (20mM) depolarized the resting membrane potential significantly. To rule out the possibility that the enhanced production of adenosine by high concentration of KCI is caused by the release of noradrenaline, secondary to the depolarization of sympathetic nerve terminals, we repeated the same experiments in the presence of 30 muM prazocin, an alpha^1-blocker. Even under this condition, introduction of 140 mM KC1 containing solution significantly enhanced the adenosine production, thereby dismissing the possibility of adenosine production mediated by noradrenaline-induced, alpha_1-receptor-mediated activation of protein kinase C activity.
These results suggest that increases in extracellular K^+ concentration depolarizes the resting membrane potential of cardiomyocytes and increase the activity of ecto-5'-nucleotidase with eventual increases of adenosine production in in situ rat's hearts. Less