Voltage Clamp Analysis of Repetitive Firing in Frog Atrial Trabeculae

The membrane currents responsible for induced pace-maker activity in frog atrial muscle were investigated using a double sucrose gap technique. The trabecula was clamped to the potential from which pace-making started (35—40 mV positive to resting potential) and immediately after that a test pulse was applied and the membrane inward current was measured. When the duration of the conditioning pulse was increased from 0.02 s to 1 s the inward current increased and reached an asymptotic value. Such a change in inward current seems to be important for the induction of repetitive firing. Mn blocked the inward current suggesting the involvement of slow Ca/Na membrane channels. A strong elevation of constant depolarizing current prevented repetitive firing, however this effect was reversed by a 3—4 fold increase in potassium ion concentration [K]D in the external medium. The outward time-independent membrane current was shown to be increased when [K]0 was elevated. Dimedrole, 10~ —5x 10~ mol.l 1 , which was observed to decrease the outward time-independent current without affecting fast and slow inward currents, prevented repetitive firing. To a lesser extent this effect was also observed with procainamide, quinidine and oxylidine. These results show that an increase in outward transmembrane time-independent current can induce repetitive firing and a decrease in outward current may prevent it. The inhibition of repetitive firing described above may be due to the inability of a small outward membrane current to repolarize the membrane perfectly so that the repetitive activation of calcium inward current is not possible. Some antiarrhythmic drugs can probably act in this manner.