Different conductance states of the bursting Na channel in guinea-pig ventricular myocytes

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Abstract
Single channel currents flowing through Na channels were studied in cell-attached patches from guinea-pig ventricular myocytes after removal of the fast component of inactivation by the S enantiomer of DPI 201-106. In addition to openings with a single channel conductance of 15 pS, two other types of events occur. A low conductance state has a single channel conductance of 5 pS, while a medium conductance state can sometimes be seen at 8 pS. These different conductance states can coexist in the same patch. The low conductance state appears to have the same kinetic properties as the high conductance state. However it is less sensitive to block by TTX. Averaged currents obtained from exclusively low conductance openings also show a decay (time constant at −30 mV of 0.8±0.4s) which is not significantly different from the decay of the high conductance channel. The average open and closed times are also similar to the values for the high conductance channel. The medium conductance state has a single channel conductance of 8 pS and a reversal potential which is similar to the high conductance channel. Closings of the high conductance state to the medium conductance state can be observed as well as openings from the medium to the high conductance state. The average current of sweeps showing only the medium conductance state has the same time course and shows a similar TTX-sensitivity as the average current of the high conductance state. Also the voltage range for steady-state activation and inactivation for the medium conductance channel matches that of the high conductance channel. Furthermore the open and closed time distributions of the medium channel are described by two exponentials. The mean open and closed tunes are not significantly different from the ones of the high conductance state. We argue that the low conductance channel is likely to be a second type of Na channel, whereas the medium conductance channel appears to be a low conductance substate of the normal bursting Na channel.