Type 1 and type 3 ryanodine receptors generate different Ca2+ release event activity in both intact and permeabilized myotubes

In this investigation we use a "dyspedic" myogenic cell line, which does no t express any ryanodine receptor (RyR) isoform, to examine the local Ca2+ r elease behavior of RyR3 and RyR1 in a homologous cellular system. Expressio n of RyR3 restored caffeine-sensitive, global Ca2+ release and causes the a ppearance of relatively frequent, spontaneous, spatially localized elevatio ns of [Ca2+], as well as occasional spontaneous, propagating Ca2+ release, in both intact and saponin-permeabilized myotubes. Intact myotubes expressi ng RyR3 did not, however, respond to K+ depolarization. Expression of RyR1 restored depolarization-induced global Ca2+ release in intact myotubes and caffeine-induced global release in both intact and permeabilized myotubes. Both intact and permeabilized RyR1-expressing myotubes exhibited relatively infrequent spontaneous Ca2+ release events. In intact myotubes, the freque ncy of occurrence and properties of these RyR1-induced events were not alte red by partial K+ depolarization or by application of nifedipine, suggestin g that these RyR1 events are independent of the voltage sensor. The events seen in RyR1-expressing myotubes were spatially more extensive than those s een in RyR3-expressing myotubes; however, when analysis was limited to spat ially restricted "Ca2+ spark"-like events, events in RyR3-expressing myotub es were larger in amplitude and duration compared with those in RyR1. Thus, in this skeletal muscle context, differences exist in the spatiotemporal p roperties and frequency of occurrence of spontaneous release events generat ed by RyR1 and RyR3. These differences underscore functional differences be tween the Ca2+ release behavior of RyR1 and RyR3 in this homologous express ion system.