EARLY REGULATION OF MEMBRANE EXCITABILITY BY RAS ONCOGENE PROTEINS

Two electrode voltage clamp conditions were used to study the early effects on ionic membrane channels of the intracellularly injected proto-oncogenic form of c-Ha-ras (c-ras) and its oncogenic counterpart v-Ha-ras (v-ras). These experiments were conducted on isolated somata of identified fully differentiated neurons of the sea snail Hermissenda. 20 min after c-ras, and 10 min after v-ras intracellular injections into type B medial photoreceptors of Hermissenda, the peak amplitude of two outward potassium currents (IA and IC), across the isolated Type B soma membrane begin to decrease. These two currents have been previously isolated by differences in activation and inactivation kinetics and their response to pharmacological blockers. c- or v-ras injections did not have any effect on a voltage-dependent inward calcium current. Reduction of IA preceded that of IC. Current reductions due to c-ras, but not to v-ras injection reversed spontaneously after 40 min. The voltage dependence of the steady state inactivation of IA shifted toward more negative potentials with ras injections. Ras-mediated cell transformations therefore, could involve, perhaps as initial events, prolonged modification of membrane currents. © 1990, The Biophysical Society. All rights reserved.