Ionic mechanisms and receptor properties underlying the responses of molluscan neurones to 5-hydroxytryptamine.

1. Molluscan neurones have been found to show six different types of response (three excitatory and three inhibitory) to the iontophoretic application of 5-hydroxytryptamine (5-HT). The pharmacological properties of the receptors and the ionic mechanisms associated with these responses have been analysed.2. Four of the responses to 5-HT (named A, A', B and C) are consequent upon an increase in membrane conductance whereas the other two (named alpha and beta) are caused by a decrease in membrane conductance.3. The A-response to 5-HT consists of a ;fast' depolarization due to an increase mainly in Na(+)-conductance; the A'-response is a ;slow' depolarization also associated with a Na(+)-conductance increase. Receptors mediating the A- and A'-depolarizations have different pharmacological properties and may exist side by side on the same neurone.4. Both the B- and C-responses are inhibitory. The B-response is a ;slow' hyperpolarization due to an increase in K(+)-conductance, the C-response is a fast hyperpolarization associated with an increase in Cl(-)-conductance.5. The alpha-response to 5-HT is a depolarization which becomes reduced in amplitude with cell hyperpolarization and reverses at -75 mV; it is caused by a decrease in K(+)-conductance. The beta-response is an hyperpolarization which increases in amplitude with cell hyperpolarization and reverses at -20/-30 mV. It results from a decrease in conductance to both Na(+) and K(+) ions.6. The receptors involved in the 5-HT responses associated with a conductance increase may be recognized by the action of specific antagonists: 7-methyltryptamine blocks only the A-receptors, 5-methoxygramine only the B-receptors and neostigmine only the C-receptors. Curare blocks the A- and C-receptors and bufotenine, the A-, A'- and B-receptors. No specific antagonists have yet been found for the 5-HT responses caused by a conductance decrease.7. The significance of the multiplicity of receptors is discussed. Their functional significance at synapses is analysed in the following paper.