Changes in subsarcolemmal sodium concentration measured by Na-Ca exchanger activity during Na-pump inhibition and beta-adrenergic stimulation in guinea-pig ventricular myocytes.
Measurement of Na-Ca exchange activity was used to examine subsarcolemmal sodium levels ([Na+]s) in single, voltage-clamped guinea-pig cardiac myocytes while Na-K pump activity was modulated pharmacologically. Changes in Nas were evaluated from phase-plane analysis of the changes in intracellular calcium, measured using the fluorescent indicators Fura-red and Fluo-3. Activation of beta-adrenoceptors with 1 microM isoprenaline resulted in activation of the cAMP-dependent chloride current, but had no effect on the calcium transient mediated via the Na-Ca exchanger, regardless of whether the Na-K pump was active or inhibited (with strophanthidin). The ability of Na-Ca exchange activity to report [Na+]s was demonstrated by the effect of changing the extracellular rubidium concentration from 1 to 5.4 mM to modulate Na-K pump activity. We suggest that beta-adrenergic stimulation does not directly affect either the Na-K pump or the Na-Ca exchanger and that the Na-Ca exchanger can be used as a sensitive indicator of changes in [Na+]s and Na-K pump activity.
Main
M J
MJ
Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK.
Grantham
C J
CJ
Cannell
M B
MB
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D005456:Fluorescent Dyes; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D012413:Rubidium / Q000494:pharmacology; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013327:Strophanthidin / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D005456:Fluorescent Dyes; D019831:Sodium-Calcium Exchanger; D013327:Strophanthidin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol; D012413:Rubidium; D002118:Calcium