Much less is known about excitatory phenomenon in mammalian smooth muscles than in skeletal or cardiac muscles. In part through work done on this project, there is now some basic information on some major ionic currents, their conductances, and equilibrium potentials in uterine smooth muscle, as well as an intestinal and a vascular smooth muscle. The method used for the voltage-clamp studies, the double-sucrose-gap technique involving multicellular strands, has serious limitations, and certain detailed information coild not be obtained. In this application, support is sought to develop an isolated single-cell preparation for voltage-clamp studies with the aim of extending and complementing knowledge already gained from the double-sucrose-gap studies. In particular, attention will be focused on fully characterized the early current, including the contributions of sodium and calcium current to the total early current. Further studies on some kinetic properties of the late current will be undertaken. The objective of these studies is to obtain the necessary quantitative data for a better understanding of the functions of mammalian smooth muscle. Support is also sought for attempts to apply voltage-sensitive dyes to the study of intrinsic pacemaker activities in the myometrium, and to the problem of conduction of impulses within the myometrium. Knowledge gained in this project could be beneficial to the understanding of the onset of labor, and its disturbances, as well as to better understanding of the actions of neurotransmitters and therapeutic agents on mammalian smooth muscle.
