title: Excitation-contraction coupling in airway smooth muscle.
abstract: Excitation-contraction (EC) coupling in striated muscles is mediated by the cardiac or skeletal muscle isoform of voltage-dependent L-type Ca(2+) 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 Ca(2+) release channel/ryanodine receptor (RyR) to release stored Ca(2+), thereby initiating muscle contraction. Specifically, in cardiac muscle following cell membrane depolarization, Ca(v)1.2 activates cardiac RyR (RyR2) through an influx of extracellular Ca(2+). In contrast, in skeletal muscle, Ca(v)1.1 activates skeletal muscle RyR (RyR1) through a direct physical coupling that negates the need for extracellular Ca(2+). 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 ( approximately 40%) by 200 mum ryanodine, thus indicating a functional coupling of L-type channels and RyRs in ASM. However, KCl still caused transient ASM contractions and stored Ca(2+) release in cultured ASM cells without extracellular Ca(2+). Further analyses of rat ASM indicated that this tissue expresses as many as four L-type channel isoforms, including Ca(v)1.1. Moreover, Ca(v)1.1 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.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Duke University, Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Wanglei
authors.initials: W
authors.lastname: Du
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: McMahon
authors.forename: Zhu-Shan
authors.initials: ZS
authors.lastname: Zhang
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Stiber
authors.forename: Gerhard
authors.initials: G
authors.lastname: Meissner
authors.forename: Jerry P
authors.initials: JP
authors.lastname: Eu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001980:Bronchi / Q000187:drug effects / Q000502:physiology*; D015220:Calcium Channels / Q000235:genetics; D020746:Calcium Channels, L-Type / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D008297:Male; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism / Q000502:physiology
chemical_list: D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel; D012433:Ryanodine