VARIABILITY IN FREQUENCY AND CHARACTERISTICS OF CA2+ SPARKS AT DIFFERENT RELEASE SITES IN RAT VENTRICULAR MYOCYTES

1. High spatial resolution confocal imaging was used to investigate sp ontaneous calcium release events (Ca2+ sparks) in isolated rat cardiac myocytes loaded with the fluorescent calcium indicator fluo-3. 2. Fre quencies of sparks at different release sites varied widely with a few sites showing sustained activities as great as 50 times the average. Sites with frequent sparks show ed more rapid recovery of activity fol lowing Ca2+ waves and locally elevated basal [Ca2+]. 3. In addition to transient sparks, some sites showed bursts of rapid flurries of spark -like events, or apparently sustained Ca2+ liberation. Bursts remained localized to individual z-lines, but adjacent sites on the same z-lin e could be 'driven' by a bursting site to generate similar activity. 4 . Individual sites showed long-term (tens of seconds) changes in 'mode s' of activity, with abrupt transitions in frequencies of sparking, an d between transient sparks and sustained bursts. These transitions wer e not associated with changes in the amplitude of the sparks. 5. We co nclude that spontaneous sparks are not stereotyped events generated wi th uniform probability at all sites. Instead, the Ca2+ release event i s variable, and some sites have a high probability of spark generation . Both factors show long-term changes at individual sites, raising the possibility that properties of fundamental Ca2+ release units may be subject to modulation.