title: Ca2+ entry, efflux and release in smooth muscle.
abstract: Control of smooth muscle is vital for health. The major route to contraction is a rise in intracellular [Ca2+], determined by the entry and efflux of Ca2+ and release and re-uptake into the sarcoplasmic reticulum (SR). We review these processes in myometrium, to better understand excitation-contraction coupling and develop strategies for preventing problematic labours. The main mechanism of elevating [Ca2+] is voltage-gated L-type channels, due to pacemaker activity, which can be modulated by agonists. The rise of [Ca2+] produces Ca-calmodulin and activates MLCK. This phosphorylates myosin and force results. Without Ca2+ entry uterine contraction fails. The Na/Ca exchanger (NCX) and plasma membrane Ca-ATPase (PMCA) remove Ca2+, with contributions of 30% and 70% respectively. Studies with PMCA-4 knockout mice show that it contributes to reducing [Ca2+] and relaxation. The SR contributes to relaxation by vectorially releasing Ca2+ to the efflux pathways, and thereby increasing their rates. Agonists binding produces IP3 which can release Ca from the SR but inhibition of SR Ca2+ release increases contractions and Ca2+ transients. It is suggested that SR Ca2+ targets K+ channels on the surface membrane and thereby feedback to inhibit excitability and contraction.
authors.affiliation: Department of Physiology, The University of Liverpool, Liverpool L69 3BX, UK.
authors.forename: A
authors.initials: A
authors.lastname: Matthew
authors.forename: A
authors.initials: A
authors.lastname: Shmygol
authors.forename: Susan
authors.initials: S
authors.lastname: Wray
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism / Q000502:physiology*; D005260:Female; D051379:Mice; D009130:Muscle, Smooth / Q000502:physiology; D009215:Myometrium / Q000378:metabolism / Q000502:physiology*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000502:physiology*; D014590:Uterine Contraction / Q000378:metabolism / Q000502:physiology*
chemical_list: D020746:Calcium Channels, L-Type; D000252:Calcium-Transporting ATPases; D002118:Calcium