The Modulated Receptor Hypothesis Revisited from the Viewpoint of Myocardial Interstitial Potential

抄録

Time- and voltage-dependent interaction of antiarrhythmic agents with target cardiac ion channels is termed the modulated receptor hypothesis. Actuaily class I agents suppress the maximum upstroke rate (V_max) of intracellular potential (V_ic) depending on the pacing cycle length (PCL) and external potassium concentration ([K⁺]_e). We examined this concept from the aspect of interstitial potential (V_is), since V_is reflects the second time derivative of V_ic. V_ic. and V_is were recorded sequentially using standard microelectrode applied to the paced and superfused guinea pig papillary muscles. In the steady state, the greatest negative deflection of V_is (V_min) was suppressed by qumldine (10 μM) In both PCL and [K⁺]_e-dependent manner just like V_max. However, quinidine-induced greater inhibition of V_min than V_max was evident at shorter PCL and greater [K⁺]_e. Based on the sequential alteration of PCL and exposure to ouabain (10 μM), different quinidine sensitivity between V_min and V_max is most likely accounted for by the activity-dependent K⁺ efflux and Na⁺-K⁺ pump-mediated K⁺ uptake (i. e., [K⁺]_e fluctuation). Thus, the modulated receptor hypothesis is concluded to be valid in terms of V_is.