title: Roles for mitochondrial and reverse mode Na+/Ca2+ exchange and the plasmalemma Ca2+ ATPase in post-tetanic potentiation at crayfish neuromuscular junctions.
abstract: We have explored the processes regulating presynaptic calcium concentration ([Ca(2+)](i)) in the generation of post-tetanic potentiation (PTP) at crayfish neuromuscular junctions, using spectrophotometric dyes to measure changes in [Ca(2+)](i) and [Na(+)](i) and effects of inhibitors of Ca(2+)-transport processes. The mitochondrial Na(+)/Ca(2+) exchange inhibitor CGP 37157 was without effect, whereas the reverse mode plasmalemmal Na(+)/Ca(2+) exchange inhibitor KB R7943 reduced PTP and Ca(2+) accumulation caused by increased [Na(+)](i). Exchange inhibitory peptide and C28R2 had opposite effects, consistent with their block of the plasma membrane Ca(2+) ATPase. All drugs except CGP 37157 reduced Ca(2+) accumulation caused by Na(+) accumulation, which occurred on block of the Na(+)/K(+) pump, acting in proportion to their effects on plasmalemmal Na(+)/Ca(2+) exchange. We find no role for mitochondrial Na(+)/Ca(2+) exchange in presynaptic Ca(2+) regulation. The plasma membrane Na(+)/Ca(2+) exchanger acts in reverse mode to admit Ca(2+) into nerve terminals during and for some minutes after tetanic stimulation, while at the same time the plasma membrane Ca(2+) ATPase operates as an important Ca(2+) removal process. The interplay of these two Ca(2+) transport processes with Na(+)-independent mitochondrial Ca(2+) fluxes and the plasmalemma Na(+)/K(+) pump determines the magnitude of tetanic [Ca(2+)](i) accumulation and potentiation of excitatory transmission, and the post-tetanic time courses of decay of elevated [Ca(2+)](i) and PTP.
authors.affiliation: Department of Molecular and Cell Biology, University of California, Berkeley, California, 94720-3200, USA.
authors.forename: N
authors.initials: N
authors.lastname: Zhong
authors.forename: V
authors.initials: V
authors.lastname: Beaumont
authors.forename: R S
authors.initials: RS
authors.lastname: Zucker
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003400:Astacoidea; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002998:Clonazepam / Q000031:analogs & derivatives* / Q000494:pharmacology; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005456:Fluorescent Dyes; D066298:In Vitro Techniques; D017136:Ion Transport / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D008928:Mitochondria / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013841:Thiazepines / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D019831:Sodium-Calcium Exchanger; D013841:Thiazepines; D010042:Ouabain; D002998:Clonazepam; C079032:CGP 37157; D012964:Sodium; D000252:Calcium-Transporting ATPases; D013890:Thiourea; D002118:Calcium