Multiple actions of 5-hydroxytryptamine on myenteric neurones of the guinea-pig ileum.

1. Intracellular recordings were made from neurones lying within ganglia isolated from the myenteric plexus of the guinea-pig ileum. 2. 5-hydroxytryptamine (5-HT) (200 nM-10 microM) was applied to 160 neurones by adding it to the perfusing solution. Depolarizations were observed in 27% of neurones, and were more likely to be observed in S-cells. Hyperpolarizations were observed in 30% of neurones, and were more likely to be seen in AH cells. 52% of neurones were unaffected. 2. 5-HT was applied to 104 neurones by micro-electrophoresis from an electrode with its tip placed close to the soma membrane. Depolarizations were observed in 35% of cells, and hyperpolarizations 13%; 10% of neurones showed biphasic responses in membrane potential and the remaining cells were unaffected. 4. The depolarizing responses to 5-HT were associated with an increase in neuronal input resistance and were probably due to inactivation of the membrane potassium conductance. The responses declined in amplitude during prolonged or repeated applications of 5-HT. 5. The hyperpolarizing responses to 5-HT were associated with a fall in neuronal input resistance and were probably due to activation of the membrane potassium conductance. These responses persisted throughout the duration of application of 5-HT and did not show marked tachyphylaxis. The hyperpolarizing responses were reversibly abolished by calcium-free solutions. 6. The depolarizing responses to 5-HT may underlie the release of acetylcholine caused by 5-HT in the guinea-pig ileum. The hyperpolarizing responses may contribute to the inhibition of the peristaltic reflex which has been observed when 5-HT is applied to the serosal aspect of the intestine.