Abstract
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.
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Selected References
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