Roles of ca2+ and pkc in the regulation of acid/base transport in
isolated proximal tubules.
Yamada, Hideomi, George Seki, Shigeo Taniguchi, Shu Uwatoko, Kazuo
Nosaka, Keiji Suzuki, and Kiyoshi Kurokawa.
FIRST DEPT. OF INTERNAL MEDICINE, TOKYO UNIVERSITY SCHOOL OF
MEDICINE, 7-3-1 HONGO, BUNKYO-KU, TOKYO 113, JAPAN AND HEALTH SERVICE
CENTER, TOKYO UNIVERSITY OF AGRICULTURE AND TECHNOLOGY, 3-8-1
HARUMICHO, FUCHU CITY, TOKYO 183, JAPAN
APStracts 3:0152F, 1996.
Roles of Ca2+ and protein kinase C (PKC) in the regulation of
acid/base transport in isolated rabbit proximal tubules were
investigated by measuring cytosolic Ca2+ concentrations ([Ca2+]i) and
cell pH (pHi) with fluorescent probes. Ionomycin (0.2 [mu]M)
increased [Ca2+]i by 200 nM, but did not affect the basolateral Na+
-HCO3- cotransporter. However, the apical Na+/H+ exchanger was
inhibited by 50 % by ionomycin, and this inhibition was abolished
either by 1, 2-bis(2-aminophenoxy)-ethane-N, N, N', N'-tetraacetic
acid, an intracellular Ca2+ chelator, or by KN-62, an inhibitor of
calcium-calmodulin-dependent protein kinase II (CaM kinase II). On
the other hand, phorbol 12-myristate 13-acetate (PMA, 0.5 [mu]M) did
not affect the apical Na+/H+ exchanger, but did stimulate the
basolateral Na+-HCO3- cotransporter by 60 - 80 %, and this
stimulation was prevented by calphostin C, an inhibitor of PKC. In
consistent with the cotransporter stimulation, PMA decreased steady
state pHi in the presence of CO2/HCO3-. These results indicate that:
(a) the acute increase in [Ca2+]i within physiological ranges
inhibits the apical Na+/H+ exchanger probably through mediation of
CaM kinase II; (b) the short-term PKC activation stimulates the
basolateral Na+-HCO3- cotransporter.
Received 20 May 1996; accepted in final form 15 August 1996.
APS Manuscript Number F154-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 19 September 1996