Membrane excitability in the neurohypophysis.

ABSTRACT

The application of patch clamp technology to the neurohypophysis has contributed significantly to our understanding of the membrane events governing neuropeptide secretion. Nerve terminals within the posterior pituitary are now known to contain three distinct K+ channel subtypes, a rapidly inactivated channel (responsible for A current), a Ca(2+)-activated K+ channel, and a delayed rectifier channel. Activation of a D2 subtype dopamine receptor reduces both the A-current and current through the Ca2+ activated K+ channels. These actions can be expected to enhance neuropeptide release. Release of nitric oxide reduces the amplitude of the A-current but enhances current through the Ca(2+)-activated K+ channel, and this would provide mechanisms for more complex modes of regulation of release. Neurohypophysial nerve terminals also express at least two types of Ca2+ channels. The first is a dihydropyridine-sensitive, "L-type" channel. The second resembles the "N-type" Ca2+ channel. Patch clamp recordings have shown that tissue culture medium conditioned by exposure to T-cells enhances this Ca2+ current. This may represent a mechanistic link between activation of the immune system and functional membrane changes within the neurohypophysis. GABA-activated Cl- channels have also been described within the neurohypophysis, and these receptors can be modulated by neuroactive steroids. One of these, the progesterone derivative allopregnanolone, changes dramatically during female reproductive transitions. Such an interaction could represent a pivotal mechanistic step in the onset of parturition, and the neurohypophysial GABA receptor may hold promise as a target of therapeutic intervention in clinical cases of preterm labor.