Journal of Physiology (1997), 502.2, pp.351-363 Role of Q-type Ca2' channels in vasopressin secretion from neurohypophysial terminals of the rat Gang Wang *, Govindan Dayanithi t, Sinmei Kim 4:, Dennis Hom §, Laszlo Nadasdi §, Ramasharma Kristipati§, J. Ramachandran §, Edward L. Stuenkel 4, Jean J. Nordmann 11, Robert Newcomb § and Jose R. Lemos *¶T * Worcester Foundation for Biomedical Research, Shrewsbury, MA 01545, USA, t CNRS UPR 9055, Biologie des Neurones Endocrines, CCIPE, Montpellier, F-34095, France, t Department of Physiology, University of Michigan, Ann Arbor, MI 48109, USA, 11 CNRS, Centre de Neurochemie, Strasbourg, F-67084, France and § Neurex Corporation, Menlo Park, CA 94025, USA 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 w-conopeptide MVIIA, but also a distinct high-affinity site for another w-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 wo-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 Ca2+-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. The regulated release of bioactive compounds from neurons is controlled by Ca+, and an understanding of chemical signalling by neurons thus requires an analysis of how the various types of Ca2P channels interact to control synaptic transmission and neurosecretion (for review, see Dunlap, Luebke & Turner, 1995). Voltage-dependent Ca2+ channels are involved in neuro- transmitter release, but the existence and specific role at central nervous system (CNS) terminals of many of the different types of Ca2+ channels is unclear. A number of studies have defined several electrophysiologically distinct voltage-activated Ca2+ channels on neuronal cell bodies (for reviews, see Bean, 1989; Tsien, Ellinor & Horne, 1991; Llina's, Sugimori, Hillman & Cherksey, 1992). The L-, N-, T- and P-type channels are the best characterized (Fox, Nowycky & Tsien, 1987; Tsien et al. 1991; Llinas et at. 1992), but other classes of channels, such as the Q- and R- types, have been revealed by molecular cloning (Snutch & Reiner, 1992; Ellinor et al. 1993; Sather, Tanabe, Zhang, Mori, Adams & Tsien, 1993) and the use of polypeptide Ca2+ channel antagonists (Olivera, McIntosh, Cruz, Luque & Grey, 1984; Hillyard et al. 1992; Ramachandran et al. 1993). The N-type Ca2+ channel is involved in the release of many 'classical' neurotransmitters, while the L-type is known to regulate the secretion of certain peptides T To whom correspondence should be addressed. 6212