ION CHANNELS IN MECHANOSENSITIVE NEURONS

Case Western Reserve University, Cleveland OH

Investigators

Linked publications & trials

Abstract

We are studying the expression of voltage-gated ion channels in the soma and terminals of baroreceptor neurons whose mechanosensitive terminals lie in the adventitia of walls of major arteries. We have proposed that these channels underlie the markedly different firing patterns of the receptors connected to unmyelinated versus myelinated fibers as they respond to changes in arterial pressure. In particular, this proposal focuses on the identification, followed by functional assessment, of the specific voltage-gated potassium channels. These channels shape the action potential and discharge patterns and they are frequent targets of neuromodulators. In the first aim we will determine which of the members of the potassium channel families, Kvl, Kv2, Kv3 and Kv4, are present in the soma of baroreceptor neurons through the use of RT-PCR, in situ hybridization and channel specific antibodies. In aim two we will move to the peripheral terminal, the actual baroreceptor, to ask whether the channels that are present in the soma are also present on the peripheral terminals. We will use immunocytochemical techniques to explore the distribution of the ion channels within the terminals of both myelinated and unmyelinated fibers using confocal microscopy. In Aim 3 we will examine the functional role of the specific potassium channels. To do this we are using anti-sense strategy in identified baroreceptor neurons. The contributions of a distinct channel to resting membrane potential, action potential and to the discharge produced by depolarization will be examined. Finally, in Aim 4 we will tie together the electrophysiological characterization with anatomical localization of the channels identified in AIMS 1-3 in mathematical models that allow us to make testable predictions for the role of each of these channels A and C baroreceptor neurons.