Role of large ca2+-activated k+ channels in regulation by
nitroprusside and anp of mesangial contraction.
Stockand, James D., and Steven C. Sansom.
Departments of Medicine and Integrative Biology, University of
Texas Medical School at Houston
APStracts 2:0401C, 1995.
The patch clamp method, in conjunction with measurements of cell
contraction, was employed to investigate activation by cGMP and
guanylyl cyclase stimulating vasodilators of large Ca-activated K
channels [BK(Ca)] in human glomerular mesangial cells. In cell
attached patches, with physiological NaCl bathing solutions, BK(Ca)
were activated transiently by nitroprusside (NP), an NO donor, atrial
natriuretic peptide (ANP) and dibutyryl cGMP (db-cGMP), reaching peak
responses between 10 to 60 sec. and decreasing to near baseline
activity within the next 120 seconds. In the presence of LY83583, a
specific inhibitor of guanylyl cyclase, BK(Ca) was activated on cell
by db-cGMP but not by NP or ANP. In all cases, the increase in
channel activity coincided with a decrease in channel amplitude,
indicating that the membrane potential was approaching EK as BK(Ca)
were activated. If membrane potential was maintained depolarized with
140 mM KCl in the bathing solution, db-cGMP induced a sustained
activation of BK(Ca). In the continued presence of db-cGMP, BK(Ca)
was further activated when 100 nM angiotensin II (AII) was added to
the bathing solution. Experiments were performed to determine the
role of BK(Ca) in the regulation by vasorelaxants of mesangial
contraction, measured as percent maximal, defined by reduction in
length induced by replacing 135 mM bath NaCl with KCl. Contraction by
AII (100 nM = 60.5%) was attenuated by NP (100 [mu]M), ANP (1.0
[mu]M) and db-cGMP (10 [mu]M) in the absence but not the presence of
iberiotoxin, a specific inhibitor of BK(Ca). These results indicate
that guanylyl cyclase stimulating vasorelaxants counteract AII
-induced contraction of MC, in part, by repolarizing the membrane
through activation of BK(Ca) channels.
Received 13 September 1995; accepted in final form 11 October
1995.
APS Manuscript Number C569-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95