Sodium channel inactivation from resting states in guinea‐pig ventricular myocytes.

1. Unitary Na+ channel currents were recorded from isolated guinea‐pig ventricular myocytes using the cell‐attached patch‐clamp technique with high [Na+] in the pipette to enhance the signal‐to‐noise ratio. 2. The probability that the channel enters the inactivated state (I) directly from resting states (C) was investigated over a wide range of membrane potentials. 3. At membrane potentials of ‐60 mV or more positive, Markov chain theory was used to estimate the probability of C‐‐‐‐I from histograms of the number of channel openings per depolarizing period. Holding potentials at least as negative as ‐136 were required to ensure that all channels resided in C prior to depolarization. 4. At membrane potentials negative to ‐60 mV, a two‐pulse protocol was employed to determine the probability of C‐‐‐‐I from the fraction of blank sweeps during the pre‐pulse with correction for missed events. 5. The probability of C‐‐‐‐I was found to be steeply voltage dependent at negative potentials, falling from 0.87 +/‐ 0.03 (mean +/‐ S.D.) at ‐91 mV to 0.42 +/‐ 0.01 at ‐76 mV. At potentials positive to ‐60 mV, this probability was less steeply voltage dependent and decayed to near zero at 0 mV. 6. Under physiological conditions, C‐‐‐‐I transitions may produce appreciable Na+ channel inactivation at diastolic potentials. At potentials above the action potential threshold, inactivation is much more likely to occur from the open state.