Similar metabolic dependence of stimulated and unstimulated myocardial slow channels.

Cardiac slow action potentials (APs) induced by isoproterenol (which is thought to increase the number of slow channels in the open state at any instant in time) are metabolically dependent. This dependence may protect the myocardium during ischemia by reducing contractility (thus sparing ATP), while allowing conduction to be nearly normal. In this study, slow APs were elicited in fast Na+ channel inactivated cardiac cells by isoproterenol, or by tetraethylammonium (TEA) which increases the net inward current without increasing the number of open slow channels. In guinea pig papillary muscles paced at 0.5 Hz, 1 mM NaCN abolished both unstimulated (TEA-elicited) and stimulated (isoproterenol-elicited) slow APs with similar time courses: the mean abolition times being 9.5 +/- 1.5 min for the unstimulated and 8.5 +/- 2.0 min for the stimulated slow APs. Pretreatment of muscles with 55 mM glucose for 30 min prolonged (abolition time of 17.5 +/- 4.5 min) or prevented (not abolished after 2 h) the NaCN abolition of slow APs. The duration of the normal fast APs was substantially reduced and the contractions ceased within 5-25 min of NaCN addition, whereas the upstroke velocity was only slightly depressed after 2 h. We conclude that unstimulated myocardial slow channels have a metabolic dependence similar to slow channels stimulated by inotropic agents.