title: Evidence for a modulatory effect of external potassium ions on ionic current mediated by the cardiac Na+-Ca2+ exchanger.
abstract: The aim of this study was to investigate whether or not the activity of the cardiac Na(+)-Ca(2+) exchanger might be directly sensitive to external K(+) concentration ([K(+)](e)). Measurements of whole-cell exchanger current (I(NaCa)) were made at 37 degrees C from guinea-pig isolated ventricular myocytes, using whole-cell patch clamp recording with major interfering conductances blocked. Changing [K(+)](e) from 0 to 5mM significantly reduced both outward and inward exchange currents in a time-dependent manner. Various [K(+)](e) between 1 and 15 mM were tested and the inhibitory effect was observed to be concentration-dependent. At steady-state, 5mM [K(+)](e) decreased the density of Ni(2+)-sensitive current by 52.8+/-4.3% (mean+/-S.E.M., n=6) and of 0Na0Ca-sensitive current by 39.0+/-4.4% (n=5). The possibility that the inhibitory effect of external K(+) on I(NaCa) might wholly or in part be secondary to activation of the sarcolemmal Na(+)-K(+) pump was investigated by testing the effect of K(+) addition in the presence of a high concentration of strophanthidin (500 microM). Ni(2+)-sensitive I(NaCa) was still observed to be sensitive to external K(+) (I(NaCa) decreased by 39.4+/-9.4%, n=4), suggesting that the inhibitory effect could occur independently of activation of the Na(+)-K(+) pump. The effect of external K(+) on I(NaCa) was verified using a baby hamster kidney (BHK) cell line stably expressing the cardiac Na(+)-Ca(2+) exchanger isoform, NCX1. Similar to native I(NaCa), NCX1 current was also suppressed by [K(+)](e). However, [K(+)](e) did not alter current amplitude in untransfected BHK cells. The effect of [K(+)](e) on I(NaCa) could not be attributed to simply adding any monovalent cation back to the external solution, since it was not reproduced by application of equimolar Li(+), Cs(+) and TEA(+). Rb(+), however, could mimic the effect of K(+). Collectively, these data suggest that external K(+) at physiologically and pathologically relevant concentrations might be able to modulate directly the activity of the cardiac Na(+)-Ca(2+) exchanger.
authors.affiliation: Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University Walk, Bristol BS8 1TD, UK. yin-hua.zhang@cardiov.ac.uk
authors.forename: Y H
authors.initials: YH
authors.lastname: Zhang
authors.forename: J C
authors.initials: JC
authors.lastname: Hancox
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000378:metabolism / Q000503:physiopathology; D002412:Cations / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D011191:Potassium Deficiency / Q000378:metabolism / Q000503:physiopathology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D019831:Sodium-Calcium Exchanger / Q000235:genetics / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D002412:Cations; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium