How Ca 2+ influx is attenuated in the heart during a “fight or flight” response

摘要

L-type Ca 2+ channels are key actors in the various scenes that lead to cardiac contractility (Reuter, 1967; Beeler and Reuter, 1970; Benitah et al., 2010). Their activation during the cardiac action potential allows Ca 2+ to enter myocytes (Beeler and Reuter, 1970; Ramos-Franco et al., 2016). This Ca 2+ influx dur- ing systole results in an increase in myoplasmic Ca 2+ concen- tration that leads to the activation of Ca 2+ release channels known as ryanodine receptor 2 (RYR2) channels (Pessah et al., 1985; Imagawa et al., 1987). RYR2s are mainly located in the terminal cisternae of the SR (Seifert and Casida, 1986; Inui et al., 1987; Lai et al., 1988). An increase in the open probability (Po) of RYR2promotesCa 2+ releasefromthe SRbya mechanism known as CICR (Ebashi and Endo, 1968; Fabiato and Fabiato, 1975; Fabiato, 1983). Ultimately, this large increase in myoplasmic Ca 2+ concentration results in cellular contraction. In this issue of JGP, Morales et al. investigate the mechanisms involved in reg- ulating Ca 2+ influx during sympathetic stimulation and, in par- ticular, the role of Ca 2+ -dependent inactivation.