AJP - Heart and Circulatory Physiology, Vol 261, Issue 6 1855-H1863, Copyright © 1991 by American Physiological Society
Caffeine-induced block of Na+ current in guinea pig single ventricular cells
Y. Habuchi, H. Tanaka, T. Furukawa and Y. Tsujimura
Department of Laboratory Medicine, Kyoto Prefectural University of Medicine, Japan.
Effects of caffeine on Na+ current (INa) were investigated in single
ventricular cells from guinea pigs using the whole cell clamp method. With
a Ca(2+)-containing internal solution (pCa 8.2), 10 mM caffeine blocked INa
by 17.5 +/- 4.6% at a -120-mV holding potential. It was accompanied by 3-
to 5-mV shifts of the steady-state inactivation curve and time
constant-voltage relationship toward hyperpolarization. The inactivation
kinetics spontaneously shifted toward hyperpolarization at 0.30 +/- 0.17
mV/min. The spontaneous shift was accompanied by a similar negative shift
of the threshold potential, whereas caffeine did not affect it. Caffeine
retarded the recovery of INa from inactivation, and a 4-mV positive shift
in the recovery potential produced a similar retardation in INa recovery
without caffeine. The INa block by caffeine was not influenced by
reinforcing the internal buffering capacities using internal solutions
containing 40 mM ethylene glycol-bis(beta-aminoethyl
ether)-N,N,N',N'-tetraacetic acid or 50 mM
N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid or by pretreating the
cell with 1 microM ryanodine. Neither pretreatment with isoproterenol or H
7 nor prestimulation of Gs protein by nonhydrolyzable GTP (GTP gamma S)
altered the effects of caffeine on INa. It is concluded that caffeine
inhibits INa and shifts the inactivation kinetics without being mediated by
changes in intracellular ionic composition or intracellular signaling
systems. Direct action on the channel proteins may be involved.
