Multiple Ca2+ channel types coexist to regulate synaptosomal neurotransmitter release.
The regulation of excitation-secretion coupling by Ca2+ channels is a fundamental property of the nerve terminal. Peptide toxins that block specific Ca2+ channel types have been used to identify which channels participate in neurotransmitter release. Subsecond measurements of [3H]-glutamate and [3H]dopamine release from rat striatal synaptosomes showed that P-type channels, which are sensitive to the Agelenopsis aperta venom peptide omega-Aga-IVA, trigger the release of both transmitters. Dopamine (but not glutamate) release was also controlled by N-type, omega-conotoxin-sensitive channels. With strong depolarizations, where neither toxin was very effective alone, a combination of omega-Aga-IVA and omega-conotoxin produced a synergistic inhibition of 60-80% of Ca(2+)-dependent dopamine release. The results suggest that multiple Ca2+ channel types coexist to regulate neurosecretion under normal physiological conditions in the majority of nerve terminals. P- and N-type channels coexist in dopaminergic terminals, while P-type and a omega-conotoxin- and omega-Aga-IVA-resistant channel coexist in glutamatergic terminals. Such an arrangement could lend a high degree of flexibility in the regulation of transmitter release under diverse conditions of stimulation and modulation.
Turner
T J
TJ
Department of Physiology, Tufts University School of Medicine, Boston, MA 02111.
Adams
M E
ME
Dunlap
K
K
D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005971:Glutamates / Q000378:metabolism*; D066298:In Vitro Techniques; D008978:Mollusk Venoms / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D013111:Spider Venoms / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects; D013574:Synaptosomes / Q000378:metabolism; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D005971:Glutamates; D008978:Mollusk Venoms; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; D002118:Calcium; D004298:Dopamine