Ca2+-transport by smooth muscle membranes and its regulation.
In smooth muscle cells two distinct Ca2+-pumps with a different subcellular localization can be demonstrated. A plasma-membrane localized Ca2+-pump with a relative molecular weight (Mr) of 140 kDa resembles the Ca2+-pump of the erythrocyte plasma membrane in the sensitivity of its phospho-intermediate towards La3+, in its calmodulin-binding capacity and in its antigenic properties. A second Ca2+-pump with a Mr of 100 kDa is situated in the endoplasmic reticulum. On the basis of its antigenicity and the degradation pattern of its phospho-intermediate the endoplasmic-reticulum Ca2+-pump is found to be homologous to the sarcoplasmic-reticulum Ca2+-pump of cardiac muscle and slow twitch skeletal muscle, but it clearly differs from the Ca2+-pump present in the sarcoplasmic reticulum of fast skeletal muscle. The endoplasmic-reticulum and the plasma-membrane Ca2+-pumps are present in both visceral and vascular smooth muscle, but tissue-and species-dependent differences in their relative amount have been observed. The endoplasmic-reticulum Ca2+-pump is regulated via phospholamban. Phosphorylation of this regulatory protein by cAMP-dependent as well as by cGMP-dependent protein kinase stimulates the endoplasmic-reticulum Ca2+-pump. On the other hand, the activity of the plasmalemmal Ca2+-pump is modulated by calmodulin, negatively charged phospholipids and membrane-receptor-binding agonists. cGMP-dependent protein kinase also exerts a stimulatory effect on the plasmalemmal Ca2+-pump. However, cGMP-dependent protein kinase does not directly phosphorylate the plasmalemmal Ca2+-pump, but by activating a phosphatidyl-inositol kinase it promotes the formation of phosphatidyl-inositol monophosphate which then acts as the final stimulator of the Ca2+-pump.
Eggermont
J A
JA
Laboratorium voor Fysiologie, Fakulteit der Geneeskunde, Katholieke Universiteit Leuven, Belgium.
Raeymaekers
L
L
Casteels
R
R
D000251:Adenosine Triphosphatases / Q000378:metabolism; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000502:physiology*; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D009130:Muscle, Smooth / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism
D015220:Calcium Channels; D000251:Adenosine Triphosphatases; D002118:Calcium