Variability of Spontaneous Ca sup 2 plus Release Between Different Rat Ventricular Myocytes Is Correlated With Na sup plus-Ca sup 2 plus Exchange and [Na sup plus] sub i

Diaz, M.E.
Cook, S.J.
Chamunorwa, J.P.
Trafford, A.W.
Lancaster, M.K.
O'Neill, S.C.

Received December 18, 1995; accepted February 1, 1996.
From the Department of Veterinary Preclinical Sciences, University of Liverpool (UK).
Correspondence to Dr D.A. Eisner, Department of Veterinary Preclinical Sciences, University of Liverpool, Liverpool L69 3BX, UK. E-mail [email protected].

Circulation Research 78(5):p 857-862, May 1996.

We have studied the factors responsible for the variation of the frequency of ``waves'' caused by spontaneous Ca sup 2 plus release in rat ventricular myocytes. The experiments were performed in isolated myocytes using the fluorescent indicators Indo-1 (to measure [Ca² plus]_i) and SBFI (to measure [Na^plus]_i). After electrical stimulation (either with action potentials or voltage-clamp pulses), some cells showed spontaneous Ca² plus release. The frequency of this release, where present, was variable. The Ca² plus content of the sarcoplasmic reticulum (SR) was measured by applying caffeine (10 mmol/L). The resulting increase of [Ca² plus]_i activated the electrogenic Na^plus-Ca² plus exchange, and the integral of this current was used to estimate the Ca² plus content of the SR. The SR Ca² plus content was significantly higher in cells that oscillated at high rates (more than 10 centered dot min^minus 1) than in those that were quiescent. The rate of removal of Ca² plus 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 plus]_i. Cells that had a high rate constant of decay of [Ca² plus]_i had a low frequency of oscillations. Measurements of [Na^plus]_i showed a positive correlation between the frequency of spontaneous SR Ca² plus release and [Na^plus]_i. After cessation of stimulation, there was a gradual decrease of [Na^plus]_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 plus release is due to variations of the rate of Ca² plus removal from the cell, which are probably due to Na^plus-Ca sup 2 plus exchange. The variability of Na^plus-Ca² plus exchange rate, in turn, is likely to result from variations of [Na^plus]_i.

(Circ Res. 1996;78:857-862.)