As a pharmacological tool, drug actions on the K- or agonist-induced contraction of smooth muscle tissues are commonly investigated. However, underlying mechanisms for generation of these contractions are not yet completely clarified. For example, the high K-induced contraction was thought to be evoked by influx of Ca during activation of the voltage dependent Ca channel in the sarcolemma and also subsequent release of Ca from the sarcoplasmic reticulum. However, investigations of the voltage dependent Ca channel using the whole cell voltage and patch clamp procedures suggested that influx of Ca occurred with short period during the depolarization, mainly due to the occurrence of inactivation of the Ca channel. On the other hand, the amount of Ca in the cytosol remained high during the depolarization, as estimated using aequorin or fura-2. The agonist-induced contraction was thought to be evoked by influx of Ca by activation of the receptor activated Ca channel with subsequently activated voltage dependent Ca channel (either lowering the threshold or as a consequence of the depolarization), and release of Ca from the sarcoplasmic reticulum following synthesis of second messengers. However, detailed mechanisms are not yet completely understand. Present knowledge concerning underlying mechanisms of the K- and agonist-induced contractions are discussed.
Vanadate, a trace element of biological tissues and fluid, has been known to be a potent inhibitor of Na, K-ATPase in various tissues. In skeletal muscle, it inhibits the Na, K-ATPase of the membrane fraction, whereas it can not inhibit the Na, K-pump in an intact preparation. It inhibits the Ca-ATPase of the sarcoplasmic reticulum and that of contractile proteins. Vanadate potentiates the contraction of some heart muscles, while it depresses the contraction in some other heart muscles. The positive and negative inotropic effects are mediated by changes in the action potential. The inhibition of Na, K-ATPase is not always involved in the inotropic actions. The inhibition of the Ca-ATPase of the sarcoplasmic reticulum and plasma membrane can be the causes of positive inotropic action. Actions on adenylate cyclase can also be the cause of inotropism. In smooth muscle, vanadate induces contractions with and/or without membrane excitation. The contractions are initiated by both the influx of extracellular Ca2+ and the release of intracellular bound Ca2+. The inhibition of Na, K-ATPase is not involved in the contraction but the inhibition of the Ca-pump of membranous systems can be the cause of the contraction. Vanadate is a useful tool for studies on the excitation-contraction coupling in muscles.