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University Department of Pharmacology, Oxford, UK.

1. Intracellular recording techniques were used to study neurotransmitter release mechanisms in postganglionic sympathetic nerve terminals of the rat isolated anococcygeus muscle. 2. Low concentrations of the N-type calcium channel blocker omega-conotoxin GVIA (omega-CgTX GVIA) irreversibly abolished excitatory junction potentials (EJPs) evoked by trains of < or = five stimuli at 10 Hz. When the frequency of stimulation was increased (10-50 Hz) trains of stimuli evoked EJPs even in the presence of 1 microM omega-CgTX GVIA. We have termed this omega-CgTX GVIA-resistant release 'residual release'. EJP amplitude in the presence of omega-CgTX GVIA depended on both the frequency and number of stimuli in a train. 3. Residual release was inhibited by the P-type calcium channel blocker omega-agatoxin IVA (100 nM). However, even in the presence of both toxins, longer trains of stimuli could still evoke neurotransmitter release. 4. Residual release was abolished by omega-conotoxin MVIIC and by the non-specific calcium channel antagonist omega-grammotoxin SIA. Therefore, it would appear that a heterogeneous population of calcium channels is involved in mediating neurotransmitter release from these sympathetic nerve terminals.

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