Stretch modulates amiloride sensitivity and cation selectivity of
sodium channels in human b lymphocytes.
Achard, Jean-Michel, James K Bubien, Dale J. Benos, and David G.
Warnock.
Departments of Medicine and Physiology & Biophysics and Nephrology
Research and Training Center, University of Alabama at Birmingham,
UAB station, Birmingham, Alabama 35294-0007 and Department of
Veterans Affairs Medical Center, Birmingham, Al 35233
APStracts 2:0282C, 1995.
Stretch-mediated regulation of amiloride-sensitive sodium channels was
examined in Epstein-Barr virus transformed human B lymphocytes.
Cation conductances were measured using whole-cell patch-clamp
techniques. Stretch activation, induced by increasing the hydrostatic
pressure of the bath solution, immediately and reversibly increased
both inward and outward ionic conductances once a threshold of 2-5 mm
H2O was reached. Ionic substitutions confirmed that stretch enhanced
membrane conductivity for both Na+ and K+. Amiloride (2 mM)
completely prevented the response to elevated hydrostatic pressure;
however, when amiloride was applied after stretch-induced activation,
the sensitivity to amiloride was dramatically decreased (IC50 20 mM).
Evidence that the currents induced by stretch were mediated by Na+
channels was provided by the lack of response to stretch in
lymphocytes from patients with Liddle's syndrome, which is caused by
expression of a truncated mutant of the b subunit of the amiloride
-sensitive Na+ channel. Pretreatment with colchicine (0.5 mM, 30 min.)
prevented stretch-induced activation, evidencing the involvement of
the cytoskeleton. These data indicate that stretch regulates the
conductance of amiloride-sensitive Na+ channels in immortalized human
B lymphocytes, and also alters its cationic selectivity and its
sensitivity to amiloride.
Received 24 April 1995; accepted in final form 19 July 1995.
APS Manuscript Number C228-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 July 1995.