Spontaneous Miniature Outward Currents in Parasympathetic Neurons: Mechanisms of Generation and Physiological Role

University Of Vermont & State Agricultural College, Burlington VT

Investigators

Abstract

0076741 Parsons Neurons generate electrical signals called action potentials, which are produced by a regulated movement of ions into and out of the neuron's surface membrane through specialized water-filled ion channels. The proposed studies will investigate how one class of membrane ion channels, the BK potassium channels, is regulated and how the activity of these BK channels affects the generation of action potential. Experiments will be done on neurons dissociated from the heart of Necturus maculosus, an aquatic amphibian. Recordings of electrical activity will be used to measure the movement of potassium ions through BK channels. The synchronous activation of a cluster of BK channels causes a small ionic current, the spontaneous miniature outward current or SMOC. The present study is designed to test what initiates and terminates SMOC activity and how this affects the generation and propagation of action potentials. BK channel activity also is dependent on fluctuations of calcium ions inside the neuron. A second aspect of the proposed study will use sophisticated optical techniques to determine what regulates the release of calcium from internal stores and how an elevation of internal calcium acts as a stimulus to direct BK channels to open. The question under study is important because information in the nervous system is conveyed by action potentials traveling along neurons. The results of the proposed studies will provide insight into the regulation of action potential generation. It is also well established that the activity of membrane ion channels, which generates action potentials, is highly regulated and complex. Thus, understanding the regulation of membrane ion channels in neurons is critical to understanding how information is processed in the nervous system. The results of the proposed studies will provide significant, new information about how one important class of ion channels, the BK channels, is regulated.