The Mg2+ block and intrinsic gating underlying inward rectification of the K+ current in guinea‐pig cardiac myocytes.

The blockade by Mg2+ and intrinsic gating of the channel, which underlie the rectification of the inward rectifier K+ current, was investigated using the oil-gap voltage clamp method in isolated guinea-pig ventricular cells. 2. The inward rectifier K+ current was isolated by subtracting trans-gap currents recorded at an extracellular K+ concentration (K+o) of 0 mM from those obtained at 14 mM K+o in the presence of a given concentration of intracellular Mg2+ (Mg2+i). The reversal potential (V0) of the difference current was near the equilibrium potential for K+ (EK). 3. On repolarization across EK, the inward rectifier K+ current showed a rapid exponential increase. The time constant decreased with increasing hyperpolarization, but it was independent of both Mg2+i and the preceding depolarization. 4. When the pre-pulse potential was made progressively positive between V0-20 and V0 + 30 mV, the amplitude of the time-dependent component became larger and the preceding current jump decreased at any Mg2+i. With pre-pulses more positive than V0 + 40 mV, the time-dependent component started from almost the zero current level at 2 microM Mg2+i. At higher Mg2+i (350, 500 and 3000 microM), however, the time-dependent component became smaller as the pre-pulse potential was made more positive than V0 + 40 mV. 5. When the membrane was depolarized from a potential of full activation at 2 microM Mg2+i, the initial jump in the outward current was ohmic and was followed by an exponential decay. The time-dependent component of the inward current, recorded on repolarization after increasing durations of the preceding depolarization, developed as the outward current decayed. The time constants of both processes were in good agreement. 6. At 500 microM Mg2+i, the outward current on depolarization was instantaneously rectified. The time-dependent component recorded on repolarization developed with prolongation of the pre-pulse with a time course slower than at 2 microM Mg2+i. The envelope time course became slower as the potential of the depolarization became more positive. 7. Lowering the temperature from 23 to 15 degrees C slowed the time-dependent current with an apparent Q10 of about 3.5 at V0. 8. Based on the experimental data, kinetic parameters were estimated for a model of Mg2+ block, which well simulated the inward-going rectification of the K+ current. 9. It is concluded that the instantaneous inward rectification on depolarization is due to the Mg2+ block at physiological Mg2+i.(ABSTRACT TRUNCATED AT 400 WORDS)