Muscarinic responses were studied in dissociated guinea-pig celiac ganglion neurons using the whole-cell voltage-clamp technique. Muscarine (0.025-1 mM; ec50 = 95 μM) administered to cells for 1.5 s evoked inward shifts in holding current in 53 of 74 cells. The amplitude of the inward current transients decreased with hyperpolarization and the null potential averaged -71 ± 3.4 mV (n = 11). The currents that underlie the responses to muscarine were examined with hyperpolarizing voltage stepping protocols to - 100 mV from a holding potential of - 30 mV. Eighty-one per cent of cells displayed voltage-dependent current relaxations characteristic of the M-potassium current. Twenty per cent of responding cells displayed no M-current but only a voltage-independent current consistent with a leak current. In the latter type of cells, the muscarine-evoked inward currents reversed near EK and became outward at more hyperpolarized potentials. Analysis of steady state I-V relationships before and after bath application of muscarine showed that the two muscarine-sensitive potassium currents were distributed differently among three types of cells: (i) with M-current (18%); (ii) with 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-current and the leak potassium current, whereas cesium (2 mM) reduced the M-current but did not affect leak current. Thus, barium reduced the amplitude of muscarinic responses by 79% but cesium reduced them by only 14%. We conclude that muscarinic responses in guinea-pig celiac neurons are produced by suppression of two K+ currents: the M-current and a muscarine-sensitive leak current. These two currents are differentially susceptible to the potassium channel blockers barium and cesium.
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