Time-Dependent Decrease in Ca²⁺-Sensitivity in “Phasic Smooth Muscle”

Abstract

Recent studies using the Ca²⁺-indicators, aequorin and fura-2, support the concept that increased intracellular Ca²⁺ ([Ca²⁺ ]_i) leads to force development in smooth muscle (for reviews, see Karaki, 1989; Somlyo and Himpens, 1989). For example, in guinea-pig taenia caecum a close correlation exists between [Ca²⁺]_i and muscle tension (Ozaki et al., 1988; Mitsui and Karaki, 1990). However, in some smooth muscles, the relationship between [Ca²⁺]_i and force development appears to depend upon the method of stimulation. For a given increase in [Ca²⁺]_i, agonists such as norepinephrine, histamine, prostaglandins, and endothelin in vascular smooth muscle (Morgan and Morgan, 1984; DeFeo and Morgan, 1985; Sato et al., 1988; Sakata et al., 1989; Mori et al., 1990; Ozaki et al., 1990a), and carbachol in trachea (Gerthoffer et al., 1990; Ozaki et al., 1990b) induce greater contractions than simple depolarization with elevated external K⁺. These findings suggest that the Ca²⁺-sensitivity of the contractile elements may be increased by certain agonists. Although the mechanism of Ca²⁺-sensitization has not been clarified, the agonist-induced activation of protein kinase C and subsequent phosphorylation of specific protein(s) may be involved.