Local calcium transients triggered by single L-type calcium channel currents in cardiac cells

Abstract

Excitation-contraction coupling was studied in mammalian cardiac cells in which the opening probability of L-type calcium (Ca2+) channels was reduced. Confocal microscopy during voltage-clamp depolarization revealed distinct local transients in the concentration of intracellular calcium ions ([Ca2+]i). When voltage was varied, the latency to occurrence and the relative probability of occurrence of local [Ca2+]i transients varied as predicted if Ca2+ release from the sarcoplasmic reticulum (SR) was linked tightly to Ca2+ flux through L-type Ca2+ channels but not to that through the Na-Ca exchanger or to average [Ca2+]i. Voltage had no effect on the amplitude of local [Ca2+]i transients. Thus, the most efficacious "Ca2+ signal" for activating Ca2+ release from the SR may be a transient microdomain of high [Ca2+]i beneath an individual, open L-type Ca2+ channel.

Ca 2+ blinks: Rapid nanoscopic store calcium signaling

“…Thus, blink detection unmasks heretofore unappreciated kinetic features of cisternal Ca 2ϩ signaling. Remarkably, t nadir of Ca 2ϩ blinks is significantly longer than the time to peak (t peak ) of sparks as measured by us in the same cells (18 Ϯ 6.2 ms, n ϭ 86; P Ͻ 0.001 vs. t nadir ) and also as reported for rat and mouse (10 ms) (12,26,33,34). These features suggest that the jSR Ca 2ϩ release flux is a time-dependent declining function, and the termination of release occurs after the peak of the spark.…”

“…The local restitution of Ca 2ϩ release was then indexed by the amplitude of the second spark relative to its corresponding first spark. It is noteworthy that, by using the spark amplitude ratio, this measurement of release recovery from refractoriness should be independent of L-type channel inactivation, because spark morphometrics are known to be unaffected by characteristics of the trigger Ca 2ϩ signal (33,34). Our results indicate that spark amplitude restitution exhibits a time constant of 187 ms, whereas local store refilling is Ϸ6-fold faster (Fig.…”

“…Electrical stimulation-activated sparks summate into global Ca 2ϩ transients (33,34). To determine whether excitation evokes blinks in parallel to sparks, we examined the excitation-evoked Ca 2ϩ release in the presence of the L-type Ca 2ϩ channel antagonist nifedipine (1 M, to reduce the density of evoked sparks for resolution of individual events).…”

Transition of spiral calcium waves between multiple stable patterns can be triggered by a single calcium spark in a fire-diffuse-fire model

“…4,5 The RyR molecules usually cluster into discrete Ca 2+ release units ͑CRUs͒ separated from one another by 0.4-2 m. 6 As the reflection of intracellular Ca 2+ release at the molecular level, Ca 2+ sparks can either occur stochastically at random locations, or, when an action potential fires, be activated in a synchronized manner summing to cell-wide Ca 2+ transients. 1,2 In some pathological conditions, spatial coupling between CRUs is enhanced so that spontaneous Ca 2+ sparks can activate neighboring CRUs via the CICR mechanism, leading to a propagating Ca 2+ release activity known as a Ca 2+ wave. 7,8 Therefore, the CICR system in cardiac cells is a typical reaction-diffusion system, in which excitable CRUs are coupled with the diffusive Ca 2+ .…”

“…This nonlinear process allows for the formation of complex spatiotemporal patterning in a variety of forms, from stochastic local Ca 2+ release events ͑puffs, sparks͒ to waves traveling across the whole cell. In cardiac myocytes, elementary Ca 2+ release events, in the stereotypical form of Ca 2+ sparks, [1][2][3] are generated by a few ryanodine receptor ͑RyR͒ Ca 2+ release channels residing on the sarcoplasmic reticulum ͑SR͒. 4,5 The RyR molecules usually cluster into discrete Ca 2+ release units ͑CRUs͒ separated from one another by 0.4-2 m. 6 As the reflection of intracellular Ca 2+ release at the molecular level, Ca 2+ sparks can either occur stochastically at random locations, or, when an action potential fires, be activated in a synchronized manner summing to cell-wide Ca 2+ transients.…”