Brain Research 884 (2000) 139–146 www.elsevier.com / locate / bres Research report Differential recruitment of N-, P- and Q-type voltage-operated calcium channels in striatal dopamine release evoked by ‘regular’ and ‘burst’ firing 1 * Paul E.M. Phillips , Jonathan A. Stamford Neurotransmission Laboratory, Academic Department of Anaesthesia and Intensive Care, Saint Bartholomew’ s and the Royal London School of Medicine and Dentistry, Royal London Hospital, Whitechapel, London E11BB, UK Accepted 12 September 2000 Abstract This study used the peptides v-conotoxin GVIA, v-agatoxin IVA and v-conotoxin MVIIC, singly and in combination, to investigate the relative involvement of N-, P- and Q-type voltage-operated calcium channels in the control of striatal dopamine release. Electrically stimulated dopamine release was measured by fast cyclic voltammetry at carbon fibre microelectrodes in rat striatal slices. The contribution of these channel subtypes was compared in dorsolateral and medial neostriatum for ‘regular’ (discrete) and ‘burst’ stimulation modalities. In dorsolateral neostriatum, a role for N-, P- and Q-type channels was demonstrated for discrete stimulations, whilst at least one other unidentified channel was also involved in dopamine release on ‘burst’ stimulations. Similarly, in the medial axis of the neostriatum, N-, P- and Q-type channels were involved in dopamine release for discrete stimulations, and N-, Q- and at least one other channel type for ‘burst’ stimulations. However, blockade of P-type channels had no effect on dopamine release for ‘burst’ stimulations in the medial axis. In both regions and stimulation paradigms, N-type channels played a greater role than P/ Q-type channels. In the medial axis of the neostriatum there was a smaller contribution by N- and P-type channels and the unidentified component, but a greater Q-type contribution to DA release. ‘Burst’ stimulations induced a lesser involvement of N- and P-type channels than discrete stimulations, and a greater role of the unidentified component. In summary, this study suggests that there is heterogeneity in the distribution of functional voltage-operated calcium channel subtypes in the neostriatum, and differences in subtype recruitment for different firing patterns. 2000 Elsevier Science B.V. All rights reserved. Theme: Excitable membranes and synaptic transmission Topic: Calcium channel structure, function and expression Keywords: Voltage-operated calcium channel; Dopamine; Neostriatum; Patterned firing; Fast cyclic voltammetry; Brain slice 1. Introduction activated when an action potential invades a neurotrans- mitter release site. Chemical neurotransmission occurs by exocytosis of VOCCs are subdivided based on their biophysical and synaptic vesicles, triggered by a rise in cytosolic calcium, pharmacological properties [2]. At present L-, N-, P-, Q-, to expel transmitters into the extracellular compartment R- and T-type channels have all been characterised, and [17]. Under physiological conditions in neurones, this is O-type channels [1] have also been proposed. achieved by entry of extracellular calcium through mem- T-type channels are activated at potentials between 265 brane-bound voltage-operated calcium channels (VOCCs), and 250 mV, show voltage-dependent inactivation during maintained depolarisation and deactivate relatively slowly upon repolarisation [31]. Conversely, L-, N-, P-, Q- and *Corresponding author. Tel.: 144-20-7377-7725; fax: 144-20-7377- R-type channels are all activated at approximately 220 7126. mV. They differ in their pharmacology and their kinetics of E-mail address: j.a.stamford@mds.qmw.ac.uk (J.A. Stamford). 1 inactivation during both maintained depolarisation and Present address: Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599-3290, USA. deactivation after repolarisation: R-type channels are the 0006-8993 / 00 / $ – see front matter 2000 Elsevier Science B.V. All rights reserved. PII: S0006-8993(00)02958-9