The cellular basis of contraction and relaxation in cardiac and vascular smooth muscle.
Changes in cytoplasmic levels of free-ionized calcium regulate the contraction and relaxation of cardiac and vascular smooth muscle. Aside from changing the intrinsic rate of energy use within the cell, an intervention that alters the strength of contraction of cardiac or vascular smooth muscle must in general alter either the intracellular calcium level, change the calcium requirements of the contractile apparatus, or exert both effects. Intracellular calcium handling is modulated by at least three other important second messengers: cyclic adenosine monophosphate, cyclic guanosine monophosphate, and inositol 1,4,5 triphosphate. These substances modulate intracellular calcium handling at multiple steps in the excitation-contraction coupling scheme. In vascular smooth muscle, diacylglycerol appears to play an important role in the regulation of myofilament calcium requirements. Intracellular calcium homeostasis is maintained through the action of sarcolemmal mechanisms that extrude calcium into the extracellular space; these mechanisms include a sodium-calcium exchange mechanism and an energy-dependent calcium pump. Abnormalities in electrophysiologic properties, sarcoplasmic reticulum function, energy use and supply, and contractile element interaction have been identified in experimental studies of animals and patients with various cardiovascular diseases. These abnormalities may be differentially affected by therapeutic agents that act on the heart or vasculature; therefore it is important to understand the underlying cellular abnormalities and subcellular actions of inotropic, vasoconstrictor, and vasodilatory drugs to apply rational therapeutics in the clinical setting.
Morgan
J P
JP
Cardiovascular Division, Beth Israel Hospital, Boston, MA 02215.
Perreault
C L
CL
Morgan
K G
KG
D000331:Aequorin; D000818:Animals; D002118:Calcium / Q000502:physiology*; D000242:Cyclic AMP / Q000502:physiology; D004075:Diglycerides / Q000502:physiology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology*; D015290:Second Messenger Systems / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*
D004075:Diglycerides; D000331:Aequorin; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D010738:Type C Phospholipases; D002118:Calcium