5-HT2 receptor-controlled modulation of medullary respiratory neurones in the cat

1. The effects of the 5-HT2 receptor agonist alpha-methyl-5-HT were studied on the membrane of expiratory (E2) and post-inspiratory (PI) neurones, by intracellular recordings in the caudal medulla of anaesthetized cats. 2. Ionophoresis of alpha-Me-5-HT depolarized membrane potential and increased action potential frequency in a majority of neurones tested. Depolarization of neurones by alpha-Me-5-HT was accompanied by increased input resistance throughout all phases of the respiratory cycle. These effects were antagonized by ionophoresis of cinanserin, a receptor-blocking agent with high affinity for 5-HT2 receptors. 3. E2 neurones were voltage clamped to measure membrane current changes induced by alpha-Me-5-HT ionophoresis. alpha-Me-5-HT induced a net inward current by reducing inspiratory-phase outward currents and increasing expiratory-phase inward currents. These changes were equivalent with steady membrane depolarization, decreased inspiratory phase membrane hyperpolarization and increased expiratory drive potential recorded from the same neurones in current clamp. 4. The effects of alpha-Me-5-HT are consistent with activation of 5-HT2 receptors on E2 and PI neurones leading to blockade of synaptically activated and persistent conductances to potassium ions.