Modulation by intracellular ATP and cyclic AMP of the slow inward current in isolated single ventricular cells of the guinea‐pig.

Abstract

Effects of ATP and of cAMP on membrane current systems were investigated in isolated single ventricular cells from guinea pig hearts by applying the suction electrode method. The intracellular milieu was dialyzed with various solutions which were perfused continuously throughout the suction pipette. The presence of ATP, cAMP and EGTA [ethyleneglycol-bis[.beta.-aminoethylether]-N,N''-tetraacetic acid] in the perfusion solution kept the plateau phase of the action potential almost intact for as long as 30 min. With depolarizing voltage-clamp pulses from holding potentials between -30 and -40 mV, the slow inward current (isi) was activated at potentials positive to -20 mV. The inactivation time course of isi was fitted by 2 exponential components in the potential range between -10 mV and +30 mV. By increasing ATP from 2 to 9.5 mM in the solution, the amplitude of isi was increased and the slow component of inactivation was accelerated. The steady-state current-voltage relationship (I-V curve) exhibited a negative slope that became steeper after increasing the ATP concentration. The current was shifted towards the outward direction between -40 mV and -10 mV and became more inward between -10 mv and +40 mV. Increase of the cAMP concentration from 30-60 .mu.M also enhanced the amplitude of isi, but the negative slope in the steady-state I-V curve was unaffected. Assuming that the concentration of free Ca2+ in the cell was well buffered at a low level by the EGTA-Ca buffer solution in the pipette, [ATP]i and [cAMP]i apparently exert a direct influence on membrane current systems of the ventricular cell.