The modulated receptor hypothesis revisited from the viewpoint of myocardial interstitial potential.
Time- and voltage-dependent interaction of antiarrhythmic agents with target cardiac ion channels is termed the modulated receptor hypothesis. Actually class I agents suppress the maximum upstroke rate (Vmax) of intracellular potential (Vic) depending on the pacing cycle length (PCL) and external potassium concentration ([K+]e). We examined this concept from the aspect of interstitial potential (Vis), since Vis reflects the second time derivative of Vic. Vic and Vis 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 Vis (Vmin) was suppressed by quinidine (10 microM) in both PCL- and [K+]e-dependent manner, just like Vmax. However, quinidine-induced greater inhibition of Vmin than Vmax was evident at shorter PCL and greater [K+]e. Based on the sequential alteration of PCL and exposure to ouabain (10 microM), different quinidine sensitivity between Vmax and Vmin 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 Vis.
Maruyama
T
T
First Department of Internal Medicine, Kyushu University.
Kaji
Y
Y
Niho
Y
Y
D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007473:Ion Channels; D008955:Models, Cardiovascular; D009206:Myocardium / Q000378:metabolism; D010210:Papillary Muscles / Q000502:physiology*; D011188:Potassium / Q000502:physiology; D011955:Receptors, Drug / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology
D000889:Anti-Arrhythmia Agents; D007473:Ion Channels; D011955:Receptors, Drug; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium