MUSCARINIC INHIBITION OF 2 POTASSIUM CURRENTS IN GUINEA-PIG PREVERTEBRAL NEURONS - DIFFERENTIATION BY EXTRACELLULAR CESIUM

Muscarinic responses were studied in dissociated guinea-pig celiac gan glion neurons using the whole-cell voltage-clamp technique. Muscarine (0.025-1 mM; EC(50) = 95 mu M) administered to cells for 1.5 s evoked inward shifts in holding current in 53 of 74 cells. The amplitude of t he inward current transients decreased with hyperpolarization and the null potential averaged -71 +/- 3.4 mV (n = 11). The currents that und erlie the responses to muscarine were examined with hyperpolarizing vo ltage stepping protocols to -100 mV from a holding potential of -30 mV . Eighty-one per cent of cells displayed voltage-dependent current rel axations characteristic of the M-potassium current. Twenty per cent of responding cells displayed no M-current but only a voltage-independen t current consistent with a leak current. In the latter type of cells, the muscarine-evoked inward currents reversed near E(K) and became ou tward at more hyperpolarized potentials. Analysis of steady state I-V relationships before and after bath application of muscarine showed th at the two muscarine-sensitive potassium currents were distributed dif ferently among three types of cells: (i) with M-current (18%); (ii) wi th leak current (18%); and (iii) with M-current and with leak current (64%). Cesium and barium were used to differentiate the M-current and the muscarine-sensitive leak current. Barium (2 mM) reduced the M-curr ent and the leak potassium current, whereas cesium (2 mM) reduced the M-current but did not affect leak current. Thus, barium reduced the am plitude of muscarinic responses by 79% but cesium reduced them by only 14%. We conclude that muscarinic responses in guinea-pig celiac neuro ns are produced by suppression of two K+ currents: the M-current and a muscarine-sensitive leak current. These two currents are differential ly susceptible to the potassium channel blockers barium and cesium.