Effect of procainamide on transmembrane action potentials in guinea-pig papillary muscles as affected by external potassium concentration

Effects of procainamide (PA), 0.18, 0.37 and 0.74 mmol/l, on the transmembrane potential were studied in isolated guinea-pig papillary muscles, superfused with modified Tyrode's solution (external K concentration, [K]_o=5.4 mmol/l) at the basic driving rate of 1 Hz. PA, at 0.37 mmol/l, significantly reduced the maximum rate of rise of action potential (\(\dot V_{\max }\)) with no change in the resting potential. When 2.7 mmol/l [K]_o of the superfusate was exchanged for 15 mmol/l [K]_o solution a decrease in \(\dot V_{\max }\) induced by 0.37 mmol/l PA became more prominent with decrease in resting potential. The reduction of \(\dot V_{\max }\) at steady state was less at lower driving rates (0.25 and 0.5 Hz) and more at higher driving rates (2–5 Hz) than at 1 Hz in 2.7, 5.4 and 10.0 mmol/l [K]_o solution. Such changes were enhanced concentration-dependently by PA at 5.4 mmol/l [K]_o. Also, the changes became more significant with an increase in [K]_o from 2.7 mmol/l to 5.4 mmol/l and then to 10.0 mmol/l. The recovery process of \(\dot V_{\max }\) proceeded with two components. The time course of the slow component seen in the \(\dot V_{\max }\) of the first response after interruption of basic driving stimulation at 1 Hz, followed an approximate monoexponential function. The time constants were 6.3, 4.4 and 5.8 s in the presence of 0.18, 0.37 and 0.74 mmol/l PA at 5.4 mmol/l [K]_o and 3.4 and 3.7 s both in the presence of 0.37 mmol/l PA at 2.7 and 10.0 mmol/l [K]_o. \(\dot V_{\max }\) values after 30 or 60 s interruption of stimulation were 80–92% of the predrug \(\dot V_{\max }\) value at 1 Hz. The time constants of the first component, estimated by the peeling-off methods at the driving rate of 0.1 Hz, were 11, 31 and 5–22 ms in the presence of 0.37 mmol/l at 5.4, 10.0 and 2.7 mmol/l [K]_o and did not differ significantly from the time constants in control preparations. The results were found to be consistent, to a certain extent, with the model proposed by Hondeghem and Katzung (1977).