CHOLECYSTOKININ-GATED CURRENTS IN NEURONS OF THE RAT SOLITARY COMPLEX IN-VITRO

1. Ionic conductances controlled by type A and type B cholecystokinin (CCK) receptors were studied in neurons of the rat nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus (DMNV), using intracellular and whole-cell patch clamp recordings in current or voltage clamp configuration during bath application of agonists (CCK8, CCK4, BC 264) and antagonists. 2. CCK(A) receptor-related inhibition was associated with a membrane hyperpolarization and a decrease in input resistance that developed 2-6 min after the arrival of drug into the extracellular medium. These effects were induced by 5 nM CCK, but not BC 264 and they were blocked by the CCK(A) antagonist, L-364,718, but not by the CCK(B) antagonist, L-365,260. 3. CCK(B) receptor-related inhibition was generated by a potassium current that reversed at a reversal potential E(rev) of -73 +/- 1 (mean +/- SE) mV with bathing potassium concentration [K+]o = 6 mM and at -88 +/- 1 with [K+]o = 3 mM. in agreement with the Nernst equation for potassium ions. 4. CCK(B) receptor-related excitation was associated with a membrane depolarization and an increase of the input resistance induced by the following agonists at threshold concentrations: CCK8 (0.2 nM) greater-than-or-equal-to BC 264 (0.4 nM) > CCK4 (10.9 nM). The increase of input resistance was abolished by L-365,260 and was maintained after blockade of the CCK(A) current by L-364,718. 5. CCK(B) receptor-related excitation, in the neurons (30% of cases) in which clear response reversal was observed, appeared to be generated by a decrease of a potassium conductance. Response showed a reversal potential E(rev) of -68 +/- 4 mV with [K+]o = 6 mM and 89 +/- 1 mV with [K+]o = 3 mM, verifying predictions from the Nernst equation applied to potassium ions. However, in 70% of cases, clear reversal was not observed at membrane potentials negative to the theoretical potassium equilibrium potential E(K). 6. In voltage clamp studies, CCK8 induced a 181 +/- 17 pA inward current associated with a 26 +/- 4% decrease in the instantaneous current (I(ins)) generated by hyperpolarizing voltage steps. This effect on I(ins) was demonstrated in the absence of effects on the outward noninactivating potassium current (I(M)) and on the inward noninactivating cationic current (I(Q)). 7. CCK(B) receptor-mediated excitation was not suppressed by cobalt, a blocker of calcium currents, and was not associated with a change of the calcium-dependent potassium current (I(K(Ca))). 8. We conclude that, in the solitary complex, CCK(A) receptors are linked to the activation of an inhibitory potassium current, whereas CCK(B) receptors reduce a potassium leak conductance, resulting in an excitation of the neuron.