[Unsolved problems on the voltage-dependent and receptor-activated contractions in smooth muscles]

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.