M-currents and other potassium currents in bullfrog sympathetic neurones.

1. Bullfrog lumbar sympathetic neurones were voltage-clamped in vitro through twin micro-electrodes. Four different outward (K(+)) currents could be identified: (i) a large sustained voltage-sensitive delayed rectifier current (I(K)) activated at membrane potentials more positive than -25 mV; (ii) a calcium-dependent sustained outward current (I(C)) activated at similar positive potentials and peaking at +20 to +60 mV; (iii) a transient current (I(A)) activated at membrane potentials more positive than -60 mV after a hyperpolarizing pre-pulse, but which was rapidly and totally inactivated at all potentials within its activation range; and (iv) a new K(+) current, the M-current (I(M)).2. I(M) was detected as a non-inactivating current with a threshold at -60 mV. The underlying conductance G(M) showed a sigmoidal activation curve between -60 and -10 mV, with half-activation at -35 mV and a maximal value (G(M)) of 84+/-14 (S.E.M.) nS per neurone. The voltage sensitivity of G(M) could be expressed in terms of a simple Boltzmann distribution for a single multivalent gating particle.3. I(M) activated and de-activated along an exponential time course with a time constant uniquely dependent upon voltage, maximizing at approximately 150 ms at -35 mV at 22 degrees C.4. Instantaneous current-voltage (I/V) curves were approximately linear in the presence of I(M), suggesting that the M-channels do not show appreciable rectification. However, the time- and voltage-dependent opening of the M-channels induced considerable rectification in the steady-state I/V curves recorded under both voltage-clamp and current-clamp modes between -60 and -25 mV. Both time- and voltage-dependent rectification in the voltage responses to current injection over this range could be predicted from the kinetic properties of I(M).5. It is suggested that I(M) exerts a strong potential-clamping effect on the behaviour of these neurones at membrane potentials subthreshold to excitation.