title: Variability of spontaneous Ca2+ release between different rat ventricular myocytes is correlated with Na(+)-Ca2+ exchange and [Na+]i.
abstract: We have studied the factors responsible for the variation of the frequency of "waves" caused by spontaneous Ca2+ release in rat ventricular myocytes. The experiments were performed in isolated myocytes using the fluorescent indicators Indo-1 (to measure [Ca2+]i) and SBFI (to measure [Na+]i). After electrical stimulation (either with action potentials or voltage-clamp pulses), some cells showed spontaneous Ca2+ release. The frequency of this release, where present, was variable. The Ca2+ content of the sarcoplasmic reticulum (SR) was measured by applying caffeine (10 mmol/L). The resulting increase of [Ca2+]i activated the electrogenic Na(+)-Ca2+ exchange, and the integral of this current was used to estimate the Ca2+ content of the SR. The SR Ca2+ content was significantly higher in cells that oscillated at high rates ( > 10 . min-1) than in those that were quiescent. The rate of removal of Ca2+ from the cytoplasm by non-SR mechanisms was measured by adding caffeine (10 mmol/L) and measuring the rate constant of decay of the resulting increase of [Ca2+]i. Cells that had a high rate constant of decay of [Ca2+]i had a low frequency of oscillations. Measurements of [Na+]i showed a positive correlation between the frequency of spontaneous SR Ca2+ release and [Na+]i. After cessation of stimulation, there was a gradual decrease of [Na+]i, which was correlated with a parallel decrease of the frequency of oscillation rate. We conclude that the variability of frequency of spontaneous SR Ca2+ release is due to variations of the rate of Ca2+ removal from the cell, which are probably due to Na(+)-Ca2+ exchange. The variability of Na(+)- Ca2+ exchange rate, in turn, is likely to result from variations of [Na+]i.
authors.affiliation: Department of Veterinary Preclinical Sciences, University of Liverpool, UK.
authors.forename: M E
authors.initials: ME
authors.lastname: Díaz
authors.forename: S J
authors.initials: SJ
authors.lastname: Cook
authors.forename: J P
authors.initials: JP
authors.lastname: Chamunorwa
authors.forename: A W
authors.initials: AW
authors.lastname: Trafford
authors.forename: M K
authors.initials: MK
authors.lastname: Lancaster
authors.forename: S C
authors.initials: SC
authors.lastname: O'Neill
authors.forename: D A
authors.initials: DA
authors.lastname: Eisner
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004558:Electric Stimulation; D006352:Heart Ventricles; D007425:Intracellular Membranes / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009991:Oscillometry; D051381:Rats; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D019831:Sodium-Calcium Exchanger
chemical_list: D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D002118:Calcium