Hiv-gp120 activates large conductance apamin-sensitive potassium channels
in rat astrocytes.
Bubien, James K., Etty N. Benveniste, and Dale J. Benos.
Departments of Medicine, Cell Biology and Physiology/Biophysics, University
of Alabama at Birmingham, Birmingham, Alabama 35294
APStracts 2:0050C, 1995.
Central nervous system (CNS) involvement usually occurs in individuals
infected with human immunodeficiency virus type 1 (HIV-1). Evidence is now
accumulating that neurons and astrocytes may be functionally compromised by
exposure to viral components or cellular factors released from HIV-1 infected
macrophages/microglia. We have previously reported that the HIV coat protein
gp120 stimulates Na+/H+ exchange in primary cultured rat astrocytes which,
ultimately, results in the activation of a potassium conductance. In this
report we characterize the electrophysiological and biophysical properties of
the channels responsible for the gp120-induced increase in K+ conductance.
These K+ channels had a relatively large unitary conductance (147 pS), were
not gated by voltage, were sensitive to changes in [H+] at their
cytosolic face, were specifically inhibited by apamin, and were insensitive
to charybdotoxin and tetraethylammonium. The activation of these channels by
gp120 is referable to cellular alkalinization subsequent to Na+/H+ exchange
stimulation; gp120 failed to activate these K+ channels in the absence of
external Na+ or in the presence of amiloride, an inhibitor of Na+/H+
exchange. Subsequent K+ loss from the astrocyte into the restricted
extracellular space surrounding neurons can then lead to neuronal
depolarization, activation of voltage-sensitive Ca2+ channels and,
eventually, cell death. Thus, abnormal activation of astrocyte K+ channels by
gp120 may contribute to the CNS pathophysiology associated with HIV-1
infection.
Received 11 August 1994; accepted in final form 7 December 1994
APS Manuscript Number C0479-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1994 The American Physiological Society.
Published in APStracts on 27 February 1995.