Strong evidence suggests that blood circulation disturbances contribute to hearing losses in loud sound- induced trauma, aging, Meni_re's disease, ototoxic drugs and some forms of sudden deafness. To understand and treat these hearing conditions, knowledge of inner ear vascular physiology is a prerequisite. Little is known about the regulating mechanisms of cochlear vessels. The long-term objective of this proposal is to increase our understanding of the cellular and subcellular physiology of these vessels and how they differ from vessels of other vascular beds. Specifically, this proposal aims to: 1) determine the membrane channels and mechanisms that cause two distinct levels of resting potentials in smooth muscle cells of cochlear spiral modiolar artery (SMA); 2) determine the actions of candidate neurotransmitters and neuropeptides on the ion channels, the responsible receptors and the intracellular signaling pathways; 3) identify the nature of neuromuscular transmission in the SMA; 4) determine how the contractile and cellular properties of the SMA differ from small arteries of the brain and intestine. These goals will be achieved by experiments using conventional and whole-cell current- and voltage-clamp recording methods on in vitro smooth muscle cells in segments of the SMA, as well as single-cell labeling and vasotone measurements. Comparative studies of contractile and membrane properties between the SMA and the arterioles from the brain and intestine will be conducted to evaluate the heterogeneity among the vessel beds. With these studies, we expect to describe the unique contractile and membrane properties, key ion- channel features, functional neuromuscular transmitters and related receptors, and mechanisms by which these functioning properties are regulated in the SMA; in addition, we expect to understand how these mechanisms of the SMA differ from those of other vessel beds. The knowledge obtained will improve our understanding of how cochlear blood flow is uniquely regulated, thus contributing to the understanding of circulation-related hearing losses and leading to prevention and treatment of these hearing conditions. The acquired knowledge should also be of significance in broad areas of cardiovascular physiology.
