New insights into the structure and function of couplons

摘要

It is widely accepted that the calcium transient in heart is a summation of many Ca~(2+) release events or sparks (Cheng et al. 1993). Each local release event is produced by a structure called a couplon (Stern et al. 1997), defined as 'the functional grouping of RyRs and dihydropyridine receptors, (DHPRs; also known as L-type Ca channels) (and other junctional SR proteins) which may act in concert during EC coupling' (Franzini-Armstrong et al. 1999). Calcium that enters the couplon through DHPRs triggers Ca~(2+) release from a cluster of RyRs (ryanodine receptors, sarcoplasmic reticulum Ca~(2+) release channels), thus producing a local release event. Each couplon obeys local control, which can explain, for example, the gradation of Ca~(2+) transients with trigger magnitude. The number of recruited couplons determines the transient amplitude. The number of DHPRs found in a couplon is of central importance, but is difficult to investigate experimentally. It seems certain that, at least in rabbits, multiple DHPRs must be present in each couplon because the probability of activation of local Ca~(2+) release events exceeds the probability that an individual DHPR will open during the action potential (Inoue & Bridge, 2003).