To study transmembrane potential (V-m) changes (Delta V-m) caused by extracellular field stimulation, V-m was recorded in 10 guinea pig papillary muscles by a double-barrel microelectrode. A 10-ms shock was delivered during the action potential plateau or during diastole. Six shock strengths (1.8 +/- 0.4, 3.8 +/- 0.7, 5.6 +/- 0.9, 7.2 +/- 1.1, 11.1 +/- 1.9, and 17.8 +/- 1.5 V/cm) were given with both polarities. The tissue was then treated with either 30 mu M tetrodotoxin (TTX; n = 5) or 30 mu M TTX plus Ca2+-free (n = 5) perfusion. For shocks during the action potential plateau, Delta V-m caused by the six potential gradients was 22.4 +/- 9.6, 43.6 +/- 17.4, 54.7 +/- 17.9, 60.4 +/- 18.1, 65.4 +/- 13.7, and 66.4 +/- 12.2 mV for shocks causing depolarization and 41.1 +/- 16.5, 68.3 +/- 22, 80.5 +/- 20.4, 84.0 +/- 19.5, 93.6 +/- 16.3, and 98.9 +/- 15.4 mV for shocks causing hyperpolarization. The relationship between Delta V-m and shock potential gradient was not linear. During diastole, hyperpolarizing shocks induced initial hyperpolarization, then depolarization followed again by hyperpolarization. A new depolarization upstroke occurred immediately after the shock. After TTX or TTX plus Ca2+-free perfusion, point stimuli 10 times diastolic threshold could not induce an action potential, but a shock field of 1.8 +/- 0.2 V/cm still induced action potentials. The peak value of depolarization measured with respect to resting potential (-87 +/- 5 mV) during the hyperpolarizing shock decreased from +14 +/- 22 before to -66 +/- 30 mV with TTX perfusion (P < 0.01). The fast upstroke rate of depolarization both during and immediately after the end of hyperpolarizing shocks was inhibited by TTX perfusion. Thus 1) the relationship between Delta V-m and shock potential gradient is not linear; 2) field but not point stimulation can induce an action potential when Na+ channels are inactivated; and 3) during diastole Na+ channels are activated twice by a 10-ms hyperpolarizing shock, once during shock-induced hyperpolarization and again immediately after the end of the shock.