MODULATION OF THE FREQUENCY OF SPONTANEOUS SARCOPLASMIC-RETICULUM CA2-MUSCLE( RELEASE EVENTS (CA2+ SPARKS) BY MYOPLASMIC [MG2+] IN FROG SKELETAL)

The modulation by internal free [Mg2+] of spontaneous calcium release events (Ca2+ ''sparks'') from the sarcoplasmic reticulum (SR) was stud ied in depolarized notched frog skeletal muscle fibers using a laser s canning confocal microscope in line-scan mode (x vs. t). Over the rang e of [Mg2+] from 0.13 to 1.86 mM, decreasing the [Mg2+] induced an inc rease in the frequency of calcium release events in proportion to [Mg2 +](-1.6). The change of event frequency was not due to changes in [MgA TP] or [ATP]. Analysis of individual SR calcium release event properti es showed that the variation in event frequency induced by the change of [Mg2+] was not accompanied by any changes in the spatiotemporal spr ead (i.e., spatial half width or temporal half duration) of Ca2+ spark s. The increase in event frequency also had no effect or. the distribu tion of event amplitudes. Finally, the rise time of calcium sparks was independent of the [Mg2+], indicating that the open time of the SR ch annel or channels underlying spontaneous calcium release events was no t altered by [Mg2+] over the range tested. These results suggest that in resting skeletal fibers, [Mg2+] modulates the SR calcium release ch annel opening frequency by modifying the average closed time of the ch annel without altering the open time. A kinetic reaction scheme consis tent with our results and those of bilayer and SK vesicle experiments indicates that physiological levels of resting Mg2+ may inhibit channe l opening by occupying the site for calcium activation of the SR calci um release channel.