On the nature of histamine-mediated slow hyperpolarizing synaptic potentials in identified molluscan neurones.

1. Standard intracellular stimulating and recording techniques were used to test the correspondence between monosynaptic post-synaptic potentials (p.s.p.s) evoked by histamine-containing C-2 neurones and responses to focally applied histamine recorded from two classes of identified post-synaptic neurones in the cerebral ganglion of Aplysia californica.2. Two types of p.s.p.s were examined: (1) a monophasic slow hyperpolarizing potential (I(s)p.s.p.) lasting 1-2 sec; and (2) a biphasic p.s.p. consisting of a fast depolarizing component <0.5 sec in duration (E(f)p.s.p.) plus a slow hyperpolarizing potential (I(s)p.s.p.) designated the E(f)I(s)p.s.p.3. Ionophoretic or pressure applied histamine mimicked both p.s.p.s and produced conductance increases in the post-synaptic neurones similar to those associated with the evoked p.s.p.s.4. The reversal potentials (E(rev)) for the I(s)p.s.p. and E(f)I(s)p.s.p., estimated by extrapolation, were -85+/-5.3, -35+/-5.5, and -83+/-8.1 mV (mean+/-S.D.), respectively. The I(s)p.s.p.s were produced by an increase in potassium conductance because their E(rev)s were shifted about 16 mV by doubling or halving the concentration of extracellular potassium and they could be eliminated by cooling or by intracellular injection of TEA ions.5. The average E(rev) values for the slow hyperpolarizing histamine responses were similar to those for the I(s)p.s.p.s; about -83 and -86 mV in neurones receiving the monophasic I(s)p.s.p.s and biphasic E(f)I(s)p.s.p., respectively.6. Cimetidine, an antihistamine drug that selectively blocks histamine receptors associated with potassium conductances in Aplysia, reversibly abolished the I(s)p.s.p.s and slow hyperpolarizing responses to focally applied histamine. In similar concentrations, cimetidine had no discernible effects on the E(f)p.s.p. and depolarizing response to histamine or on several different types of p.s.p.s mediated by the C-2 neurones.7. It is proposed that the I(s)p.s.p.s are mediated by histamine released from the C-2 neurones.