title: Effects of Na+-Ca2+ exchanger activity on the alpha-amino-3-hydroxy-5-methyl-4-isoxazolone-propionate-induced Ca2+ influx in cerebellar Purkinje neurons.
abstract: Variations in intracellular calcium activity ([Ca2+]i) play crucial roles in information processing in Purkinje neurons such as synaptic plasticity. Although Na+-Ca2+ exchanger (NCX) has been shown to participate in the regulation of homeostasis and secretion in neuronal cells, the physiological role of NCX in Purkinje neurons, such as a role in cerebellar synaptic plasticity, is not well understood. NCX in acutely dissociated rat Purkinje neurons was identified by double staining with anti-calbindin D-28k antibody and anti-NCX antibody. The physiological activity of NCX was examined by measuring transient intracellular Ca2+ changes resulting from the Ca2+ influx via reverse mode of NCX (with 0 mM Na+/2.5 mM Ca2+ solutions) and the efflux via the forward mode of NCX (with 140 mM Na+/0 mM Ca2+ solutions). This transient increase in Ca2+ concentration was not elicited in the cells pretreated with NCX antisense oligodeoxynucleotides. And the Ca2+ influx resulting from the reverse mode of NCX was significantly reduced by 2-[2-[4-(4-nitrobenyloxy) phenyl] ethyl] isothiourea methanesulfonate, while the Ca2+ efflux via forward mode was inhibited by bepridil. The physiological role of NCX in synaptic function was studied by measuring Ca2+ transients induced by alpha-amino-3-hydroxy-5-methyl-4-isoxazolone-propionate (AMPA) receptor activation. This AMPA-evoked response was decreased with the inhibition of NCX forward mode and also, to less degree, with the inhibition of reverse mode. In antisense oligodeoxynucleotides pretreated cells, the AMPA-evoked response was also reduced, as was the case in NCX-inhibitor treated cells. The inhibition of NCX activity had depressant effects on Ca2+ transients induced by AMPA receptor activation. These results suggest that NCX plays a physiological role in modulating the activity of cerebellar Purkinje neurons, such as synaptic plasticity, via interaction with AMPA receptors in Purkinje neurons.
authors.affiliation: Department of Physiology and Biophysics, College of Medicine, Inha University, 253, Yonghyun-Dong, Nam-Ku, Incheon, 402-751 Korea.
authors.forename: Y T
authors.initials: YT
authors.lastname: Kim
authors.forename: Y J
authors.initials: YJ
authors.lastname: Park
authors.forename: S Y
authors.initials: SY
authors.lastname: Jung
authors.forename: W S
authors.initials: WS
authors.lastname: Seo
authors.forename: C K
authors.initials: CK
authors.lastname: Suh
mesh_terms: D060848:Agatoxins; D000818:Animals; D000831:Animals, Newborn; D015764:Bepridil / Q000494:pharmacology; D064026:Calbindins; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D003952:Diagnostic Imaging / Q000379:methods; D004347:Drug Interactions; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005455:Fluorescent Antibody Technique / Q000379:methods; D018698:Glutamic Acid / Q000494:pharmacology; D007555:Isoxazoles / Q000494:pharmacology*; D018613:Microscopy, Confocal / Q000379:methods; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology*; D011689:Purkinje Cells / Q000187:drug effects* / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000502:physiology*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D060848:Agatoxins; D064026:Calbindins; D002121:Calcium Channel Blockers; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007555:Isoxazoles; D016376:Oligonucleotides, Antisense; D011073:Polyamines; D011422:Propionates; D011810:Quinoxalines; D064030:S100 Calcium Binding Protein G; D026941:Sodium Channel Blockers; D019831:Sodium-Calcium Exchanger; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; C076532:agatoxin-489; C081662:alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionate; D018698:Glutamic Acid; D015764:Bepridil; D012964:Sodium; D013890:Thiourea; D002118:Calcium