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.
Collin
C
C
National Institutes of Health, Laboratory of Molecular and Cellular Neurobiology, Bethesda, Maryland 20892.
Papageorge
A G
AG
Sakakibara
M
M
Huddie
P L
PL
Lowy
D R
DR
Alkon
D L
DL
D000818:Animals; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D004594:Electrophysiology; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000502:physiology*; D010786:Photoreceptor Cells / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000502:physiology*; D012908:Snails; D012964:Sodium / Q000378:metabolism
D015221:Potassium Channels; D012964:Sodium; D016283:Proto-Oncogene Proteins p21(ras); D011188:Potassium; D002118:Calcium