Modification of Ca2+ Regulatory Systems

This chapter discusses mechanisms for modifying Ca²⁺ regulatory systems in the myometrium, it is necessary first to review the cellular systems controlling intracellular Ca²⁺. The uterine relaxants isoproterenol and relaxin attenuate the oxytocin-stimulated increases in Cai²⁺ and phosphoinositide turnover. Regulation of Ca²⁺ channels appears to be an important mechanism by which contractants and relaxants mediate their effects in smooth muscle. In a number of smooth muscle preparations, contractants increase Ca²⁺ influx even when the tissue has already been depolarized or pretreated with voltage-operated Ca²⁺ channel (VOC) blockers, suggesting mechanisms other than activation of VOCs, such as activation of receptor-operated Ca²⁺ channels. In addition to acute regulation of Ca²⁺ channels, channel expression may also be regulated by hormones. inositol-1,4,5-trisphosphate (IP₃) is an important second messenger mediating release of Ca²⁺ from intracelluar organelles by hormones and neurotransmitters. The purified IP₃ receptor from a number of sources forms Ca channels in lipid vesicles and bilayers.