FIGURE 3.

Alcohol action on smooth muscle myocyte contractility. E-C coupling in smooth muscle myocytes occurs via calcium-induced calcium release (CICR) mechanisms as seen in cardiomyocytes. However, Ca²⁺-release leading to contraction occurs signficantly via IP₃Rs. DHPRs are activated by depolarization of the smooth muscle myocyte membrane causing RyR2 and IP₃Rs to release a small amount of Ca²⁺ into the cytoplasm. Unlike striated myocytes, troponin and tropomyosin are not involved in the coupling of myosin and actin; instead, Ca²⁺ ions bind to CAM which phosphorylates MLCK leading to its association with actin, resulting in a “power stroke”. In vascular smooth muscle, RyR2 (and possibly RyR3 as well)-induced release of Ca²⁺ generates the so-called “sparks” which activate BK channels, leading to membrane repolarization and vasodilation. In smooth muscle myocytes, alcohol has been reported to cause both contraction and relaxation according to the type of muscle (vascular/ non-vascular), concentration of alcohol used and other conditions. The effects of acute ethanol consumption/administration include: increased ROS and NO^• production (aorta, coronary, cerebral and mesenteric arteries), decreased BK channel activity (aorta, cerebral arteries), increased Kv channel activity (coronary arteries), decreased RyR activity (cerebral arteries), increased EDGF activity (mesenteric arteries) and increased PLA2 activity (bladder). Many of these events are exacerbated after chronic ethanol consumption/administration which additionally causes increased uterine artery diameter, decreased ROCK pathway activity (lungs), increased ET-1 levels (carotid arteries, vas deferens) and dysregulation of nutrient and water absorption in the gut. Abbreviations: BK channels, big K⁺ channels; CSA, cross sectional area; DHPRs, dihydropyridine receptors; EDGF, endothelium-dependent hyperpolarizing factor; ET-1, endothelin 1; IP₃R, inositol trisphosphate receptor; NCX, Na⁺- Ca²⁺-exchanger; PLA2, phospholipase A2; PLB, phospholamban; ROS, reactive oxygen species; ROCK, Rho-associated protein kinase; RyR, ryanodine receptors; SERCA, SR Ca²⁺ transport ATP-ase; SR, sarcoplasmic reticulum; STOCs, Spontaneous Transient Outward Currents; t-tubules, transverse tubules.