Combined effects of rate membrane potential, and drugs on maximum rate of rise (Vmax) of action potential upstroke of guinea pig papillary muscle.

We studied the effect of increasing the rate of stimulation on the maximum rate of rise of the action potential upstroke (Vmax) in guinea pig papillary muscles at various resting membrane potentials and after the addition of quinidine and lidocaine to the perfusate. Increasing rate caused a decrease in Vmax due to interaction of three factors: (1) a metabolic factor, presumably resetting of the Na-K pump, which caused a decrease in Vmax at all levels of resting potential between -90 and -60 mV, (2) a transient decrease in resting potential which influenced Vmax when the resting potential was less negative than approximately -80 mV, and (3) the recovery characteristics of Vmax which contributed to the decrease in this variable when rate was faster than 5/sec. As a result of these factors the steady state curve relating membrane potential to Vmax was itself rate-dependent. Lidocaine and quinidine exaggerated the rate-dependent decrease in Vmax; however, their effects differed. The effect of quinidine was consistent with its known depressant effect on the Na-K pump. The lidocaine effect was consistent with a slowing of recovery of Vmax. Our results help to explain the effects of an increase in rate on Vmax and conduction velocity in normal, partially depolarized, and drug-treated fibers