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 α and β) 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 α-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 β-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.