Excitation-Ca¥ release coupling is a pivotal event in cardiac function. During membrane depolarization, sarcolemmal Ca¥ influx through the voltage-operated L_type Ca¥ channels triggers the sarcoplasmic reticulum (SR) to release Ca¥ via the Ca¥-induced Ca¥ release (CICR) mechanism (Fabiato, 1983). The resultant cytosolic Ca¥ transient activates myofilament proteins and initiates contraction. Cardiac relaxation ensues when the elevated cytoplasmic Ca¥ is resequestered by the SR Ca¥ pump, or, to a lesser extent, extruded via the sarcolemmal Na¤-Ca¥ exchanger. In order to meet the body's variable circulatory demands, cardiac excitation-contraction (EC) coupling is constantly modulated by an array of physiological mechanisms. Driven by sympathetic neurotransmitters and adrenal hormones, â_adrenergic receptor (âAR) signalling interacts with virtually all constituents of the EC coupling cascade, including the L_type Ca¥ channel current (ICa) (Tsien et al. 1986;Xiao & Lakatta, 1993), SR Ca¥ release channels/ ryanodine receptors (RyRs) (Yoshida et al. 1992;, phospholamban (PLB) (Lindemann et al. 1983;Kuschel et al. 1999a), and contractile myofilaments (Rapundalo et al. 1989; Kuschel et al. 1999b). Additionally, â_adrenergic stimulation may modulate other sarcolemmal ionic currents, such as K¤ currents (Scamps, 1996), and electrogenic transporters, such as Na¤-Ca¥ exchanger (in non-mammalian species) (Shuba et al. 1998), to alter the

Investigating how calcium release from the endoplasmic reticulum (ER) is triggered and coordinated is crucial to our understanding of how oligodendrocyte progenitor cells (OPs) develop into myelinating cells. Sparks and puffs represent highly localized Ca 2ϩ release from the ER through ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP 3 Rs), respectively. To study whether sparks or puffs trigger Ca 2ϩ waves in OPs, we performed rapid high-resolution line scan recordings in fluo-4-loaded OP processes. We found spontaneous and evoked sparks and puffs, and we have identified functional cross talk between IP 3 Rs and RyRs. Local events evoked using the IP 3 -linked agonist methacholine (MeCh) showed significantly different morphology compared with events evoked using the caffeine analog 3,7-dimethyl-1-propargylxanthine (DMPX). Pretreatment with MeCh potentiated DMPX-evoked events, whereas inhibition of RyRs potentiated events evoked by low concentrations of MeCh. Furthermore, activation of IP 3 Rs but not RyRs was critical for Ca 2ϩ wave initiation. Using immunocytochemistry, we show OPs express the specific Ca 2ϩ release channel subtypes RyR3 and IP 3 R2 in patches along OP processes. RyRs are coexpressed with IP 3 Rs in some patches, but IP 3 Rs are also found alone. This differential distribution pattern may underlie the differences in local and global Ca 2ϩ signals mediated by these two receptors. Thus, in OPs, interactions between IP 3 Rs and RyRs determine the spatial and temporal characteristics of calcium signaling, from microdomains to intracellular waves.

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