Cyanide inhibits the Na+/Ca2+ exchanger in isolated cardiac pacemaker cells of the cane toad.
The effects of the metabolic inhibition on the activity of the Na+/Ca2+ exchanger (NCX) were studied in single isolated pacemaker cells from the cane toad. Ca2+ influx on NCX (reverse mode) was estimated by measuring the increase in intracellular calcium concentration ([Ca2+]i) in response to extracellular Na+-free solution. After application of 2 mM sodium cyanide for 3-5 min, the peak [Ca2+]i in Na+-free solution was significantly decreased from 377+/-42 nM to 260+/-46 nM, suggesting inhibition of NCX. To study Ca2+ efflux on NCX (forward mode), we recorded the tail currents on repolarization which were abolished by Ni2+ and by Na+-free solution. Cyanide decreased the amplitude of tail currents by 36+/-3%. To investigate the intrinsic properties of NCX during the metabolic inhibition, we used rapid application of caffeine to trigger sarcoplasmic reticulum Ca2+ release, which then stimulates NCX current (I(NCX) ). Both the caffeine-induced peak [Ca2+]i and the peak I(NCX) were reduced by cyanide exposure. When I(NCX) was plotted against [Ca2+], the slope of the decay phase was decreased in the presence of CN- to 44+/-8% of control, indicating that for a given [Ca2+]i there was less I(NCX) produced. These results show that cyanide (CN-) inhibits NCX activity at least partly through changes in the intrinsic properties of NCX. The inhibition of NCX probably contributes to the slower firing rate of pacemaker cells in CN-.
Ju
Yue-kun
YK
Department of Physiology, Institute for Biomedical Research, University of Sydney, F13, Sydney, NSW, Australia.
Allen
David G
DG
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects*; D002024:Bufo marinus; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D009206:Myocardium / Q000166:cytology*; D011042:Poisons / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D012966:Sodium Cyanide / Q000494:pharmacology*; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors*
D011042:Poisons; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D012966:Sodium Cyanide; D002118:Calcium