Cyanide inhibits the Na+/Ca2+ exchanger in isolated cardiac pacemaker cells of the cane toad.

ABSTRACT

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-.