THE EFFECT OF ATROPINE ON THE ACTIVATION OF 5-HYDROXYTRYPTAMINE(3) CHANNELS IN RAT NODOSE GANGLION NEURONS

It has been suggested that changes in brain 5-hydroxytryptamine(3) rec eptor function may contribute to some behavior disorders, such as anxi ety, schizophrenia and drug abuse. We are using the whole-cell version of the patch-clamp technique to study the function of 5-hydroxytrypta mine(3) channels in neurons freshly dissociated from rat nodose gangli on. In these cells, 5-hydroxytryptamine elicits an inward current over the concentration range of 0.25-100 mu M (EC(50) = 2.62 mu M) by acti vating 5-hydroxytryptamine(3) receptors. The muscarinic cholinergic an tagonist atropine reduced the amplitude of 5-hydroxytryptamine activat ed inward current in a concentration-dependent manner. Other muscarini c antagonists, scopolamine, dexetimide, the M1 muscarinic receptor ant agonist pirenzepine, the M(2), receptor antagonist methoctramine and t he M(3) receptor antagonist 4-DAMP methiodide also inhibited 5-hydroxy tryptamine-induced inward current. Atropine did not appear to change t he reversal potential of this current. In the presence of 5 mu M atrop ine, the concentration-response curve for 5-hydroxytryptamine current was shifted to the right in a parallel fashion. The EC(50) value for 5 -hydroxytryptamine was increased from 2.62 to 8.76 mu M. Schild plots of increasing atropine and 5-hydroxytryptamine concentrations revealed a pA(2) value of 5.74 for atropine (apparent K-D = 1.8 mu M). These o bservations suggest that atropine competitively antagonizes the activa tion of a receptor for the neurotransmitter serotonin, a novel action of muscarinic antagonists in the nervous system. This effect of atropi ne may contribute to the clinical symptoms seen in severe atropine int oxication.