Role of Q-type Ca2+ channels in vasopressin secretion from neurohypophysial terminals of the rat.
1. The nerve endings of rat neurohypophyses were acutely dissociated and a combination of pharmacological, biophysical and biochemical techniques was used to determine which classes of Ca2+ channels on these central nervous system (CNS) terminals contribute functionally to arginine vasopressin (AVP) and oxytocin (OT) secretion. 2. Purified neurohypophysial plasma membranes not only had a single high-affinity binding site for the N-channel-specific omega-conopeptide MVIIA, but also a distinct high-affinity site for another omega-conopeptide (MVIIC), which affects both N- and P/Q-channels. 3. Neurohypophysial terminals exhibited, besides L- and N-type currents, another component of the Ca2+ current that was only blocked by low concentrations of MVIIC or by high concentrations of omega-AgaIVA, a P/Q-channel-selective spider toxin. 4. This Ca2+ current component had pharmacological and biophysical properties similar to those described for the fast-inactivating form of the P/Q-channel class, suggesting that in the neurohypophysial terminals this current is mediated by a 'Q'-type channel. 5. Pharmacological additivity studies showed that this Q-component contributed to rises in intraterminal Ca2+ concentration ([Ca2+]i) in only half of the terminals tested. 6. Furthermore, the non-L- and non-N-component of Ca(2+)-dependent AVP release, but not OT release, was effectively abolished by the same blockers of Q-type current. 7. Thus Q-channels are present on a subset of the neurohypophysial terminals where, in combination with N- and L-channels, they control AVP but not OT peptide neurosecretion.
Wang
G
G
Worcester Foundation for Biomedical Research, Shrewsbury, MA 01545, USA.
Dayanithi
G
G
Kim
S
S
Hom
D
D
Nadasdi
L
L
Kristipati
R
R
Ramachandran
J
J
Stuenkel
E L
EL
Nordmann
J J
JJ
Newcomb
R
R
Lemos
J R
JR
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002417:Cattle; D002462:Cell Membrane / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009411:Nerve Endings / Q000502:physiology; D010121:Oxytocin / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D013111:Spider Venoms / Q000494:pharmacology; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020960:omega-Conotoxins; D001127:Arginine Vasopressin; C075851:omega-conotoxin-MVIIC; D010121:Oxytocin; C078452:ziconotide; D002118:Calcium