Excitation-contraction coupling in airway smooth muscle

Excitation-contraction (EC) coupling in striated muscles is mediated by the cardiac or skeletal muscle isoform of voltage-dependent L-type Ca2+ channel (Ca(v)1.2 and Ca(v)1.1, respectively) that senses a depolarization of the cell membrane, and in response, activates its corresponding isoform of intracellular Ca2+ release channel/ryanodine receptor (RyR) to release stored Ca2+, thereby initiating muscle contraction. Specifically, in cardiac muscle following cell membrane depolarization, Cav1.2 activates cardiac RyR (RyR2) through an influx of extracellular Ca2+. In contrast, in skeletal muscle, Cav1.1 activates skeletal muscle RyR (RyR1) through a direct physical coupling that negates the need for extracellular Ca2+. Since airway smooth muscle (ASM) expresses Ca(v)1.2 and all three RyR isoforms, we examined whether a cardiac muscle type of EC coupling also mediates contraction in this tissue. We found that the sustained contractions of rat ASM preparations induced by depolarization with KCl were indeed partially reversed (similar to 40%) by 200 mu M ryanodine, thus indicating a functional coupling of L-type channels and RyRs in ASM. However, KCl still caused transient ASM contractions and stored Ca2+ release in cultured ASM cells without extracellular Ca2+. Further analyses of rat ASM indicated that this tissue expresses as many as four L-type channel isoforms, including Cav1.1. Moreover, Cav1.1 and RyR1 in rat ASM cells have a similar distribution near the cell membrane in rat ASM cells and thus may be directly coupled as in skeletal muscle. Collectively, our data implicate that EC-coupling mechanisms in striated muscles may also broadly transduce diverse smooth muscle functions.