Sarcoplasmic reticulum Ca ²⁺ release flux underlying Ca ²⁺ sparks in cardiac muscle

Abstract

Discrete events of Ca 2؉ release from the sarcoplasmic reticulum (SR) have been described in cardiac, skeletal, and smooth muscle. In skeletal muscle these release events originate at individual channels. In cardiac muscle, however, it remains a question of debate whether localized Ca 2؉ release transients, termed Ca 2؉ sparks, originate from single release channels or multiple channels clustered in close vicinity. Generalizing methods used earlier to describe cellaveraged Ca 2؉ release, we derived, as a function of space and time, the f lux of Ca 2؉ release that underlies Ca 2؉ sparks. Using the method to analyze spontaneous sparks recorded with confocal microscopy in dissociated cat atrial cells, we obtained in most cases single sparks of Ca 2؉ release that appear to originate from approximately 1-m-wide regions. In many cases, doublets, triplets, and greater groups of release sparks were observed. This multiplicity, the estimated release f lux magnitude, and existing data on the structure of junctions between SR and plasmalemma suggest that individual release sparks result from the opening of multiple Ca 2؉ release channels clustered within discrete SR junctional regions.

Inositol 1,4,5-trisphosphate receptors modulate Ca2+ sparks and Ca2+ store content in vas deferens myocytes

“…The results presented so far have demonstrated that blockade of IP 3 Rs elevates Ca 2ϩ store content in guinea pig vas deferens myocytes. This implies that background activation of IP 3 Rs by endogenous IP 3 normally limits store content by activating a leak pathway.…”

“…We investigated the effect of IP 3 R blockade on SR store content and Ca 2ϩ sparks in smooth muscle from the vas deferens. Our results indicate that basal activation of IP 3 Rs provides a Ca 2ϩ leak pathway limiting Ca 2ϩ stores in this tissue. Blockade of this leak pathway increased store content and Ca 2ϩ spark activity.…”

“…The STOC data are also summarized as means Ϯ SE, and the statistical significance of differences between means was assessed with a paired or unpaired t-test as indicated. 3 R blockade on spontaneous Ca 2ϩ sparks. Line-scan images of myocytes from the vas deferens loaded with fluo 4 and superfused with physiological external [Ca 2ϩ ] often demonstrated spontaneous and localized [Ca 2ϩ ] i rises with spatiotemporal characteristics similar to those of Ca 2ϩ sparks described in other smooth muscle cells (14).…”

“…The resulting Ca 2ϩ signal may be generalized or restricted to a specific region of the cell. Transient, local release events known as "Ca 2ϩ sparks" are generated by the spontaneous opening of a cluster of RyR channels (3,15). These sparks represent fundamental signaling events whose spatial and temporal summation generates global increases in intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) during excitation-contraction coupling in cardiac and skeletal muscle (6,29).…”

Emerging roles of inositol 1,4,5-trisphosphate signaling in cardiac myocytes

“…Ca 2+ sparks represent Ca 2+ release from a restricted number of clustered RyRs opening in concert [81]. It is well established that Ca 2+ sparks represent the elementary Ca 2+ release events that spatially and temporally summate to produce the global Ca 2+ transient during cardiac excitation-contraction coupling.…”