Calcium homeostasis in smooth muscle cells.
Calcium triggers muscle contraction and is a second messenger of hormones and growth factors that regulate metabolism, gene expression, and secretion in smooth muscle cells (SMC). SMC contain dozens of proteins that bind Ca2+ either to buffer changes in ionized calcium or to elicit a cellular response such contraction or secretion. Although there practically an infinite supply of Ca2+ in extracellular medium, SMC respond to a variety of stimuli by mobilizing Ca2+ accumulated in the sarcoplasmic reticulum (SR), where most cellular Ca2+ resides. The SR of smooth muscle resembles the endoplasmic reticulum of nonmuscle cells and accumulates Ca2+ via the sarcoendoplasmic reticulum Ca2+ adenosine triphosphatase (ATPase). Stimuli, such as angiotensin II, produce inositol 1,4,5,-trisphosphate (IP3), which regulates a Ca2+ channel of the SR. IP3 binding opens the channel and produces a "spike" in the cytoplasmic concentration of free Ca2+ ([Ca2+]i). The spike is largely due to the release of stored Ca2+ because hormonal stimulation produces similar spikes in the presence and absence of extracellular Ca2+. Ca2+ ejection from the cell, rather than reaccumulation by the SR, is responsible for rapidly decreasing [Ca2+]i from the peak level produced by the stimulus. Release of SR Ca2+ and activation of plasma membrane Ca2+ efflux mechanisms markedly decrease total cell Ca2+. Two independent Ca2+ transporters in the plasma membrane, the Na(+)-Ca2+ exchanger and the Ca2+ ATPase, actively eject Ca2+ from SMC. The Na(+)-Ca2+ exchanger is largely responsible for the acute phase of Ca2+ ejection, whereas the plasma membrane Ca2+ ATPase contributes to the sustained increase in Ca2+ efflux from stimulated SMC. Following Ca2+ release from the SR and ejection from the cell, Ca2+ enters via channels, which sustain a modest increase in [Ca2+]i and a gradual refilling of the SR. Mitochondria have an important role in intracellular Ca2+ signaling. Mitochondrial metabolism is highly responsive to transient increases in [Ca2+]i, although mitochondria are not a Ca2+ repository. Ca2+ uptake by mitochondria is driven by the highly favorable electrochemical potential difference across the inner membrane. Mitochondria actively expel Ca2+ via a H(+)-Ca2+ or Na(+)-Ca2+ exchanger. Ca2+ uptake and ejection by mitochondria contributes to temporal and spatial oscillations in [Ca2+]i. accelerated Ca2+ cycling between the Sr, cytoplasm, mitochondria, and the environment is a hallmark of cell stimulation.
Smith
J B
JB
Department of Pharmacology and Toxicology, School of Medicine, University of Alabama at Birmingham 35294-0019, USA.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008931:Mitochondria, Muscle / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D002118:Calcium