Omega-conotoxin GVIA-resistant neurotransmitter release in postganglionic sympathetic nerve terminals.
Intracellular recording techniques were used to study neurotransmitter release in the guinea-pig isolated vas deferens. Low concentrations of the irreversible and selective N-type calcium channel blocker omega-conotoxin GVIA have previously been shown to block excitatory junction potentials evoked by low frequencies (< or = 1 Hz) of nerve stimulation. Here we report a component of action potential-evoked release which is insensitive to high concentrations of omega-conotoxin GVIA. We have termed this component "residual release" and show (i) it is positively frequency-dependent, (ii) its magnitude is dependent on both the train length and interval between trains, (iii) "residual release" can be modulated through prejunctional alpha 2-adrenoceptors and (iv) "residual release" is insensitive to many calcium entry blockers but abolished by omega-grammotoxin SIA and cadmium ions. Although noradrenaline is released by nerve action potentials, residual excitatory junction potentials were abolished by alpha,beta-methylene-ATP and therefore resulted entirely from the actions of neuronally released ATP acting through postjunctional P2x-purinoceptors. The results suggest that calcium entry through a novel, pharmacologically uncharacterized voltage-dependent calcium channel is responsible for "residual release" in sympathetic nerve terminals. It seems that in response to single or short trains of nerve action potentials, N-type calcium channels dominate the release process. However, at higher frequencies other voltage-dependent calcium channels are recruited and these may have an important role to play in triggering the mechanisms underlying frequency-dependent facilitation.
Smith
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University Department of Pharmacology, Oxford, U.K.
Cunnane
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D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004558:Electric Stimulation; D005728:Ganglia, Sympathetic / Q000378:metabolism*; D006168:Guinea Pigs; D008297:Male; D009411:Nerve Endings / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D018377:Neurotransmitter Agents; D010455:Peptides; D010456:Peptides, Cyclic; C082807:omega-grammotoxin SIA; D015016:Yohimbine; D000255:Adenosine Triphosphate; D020866:omega-Conotoxin GVIA; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium