Effects of ryanodine and BAY K 8644 on membrane properties and conduction during simulated ischemia.
We studied the effect of 1.0 microM ryanodine and 0.1 microM BAY K 8644 (putative modulators of intracellular calcium) on the changes in action potential characteristics, cellular coupling, and longitudinal conduction induced by simulated ischemia (9.0 mM K, 6.5 pH, 0 glucose, 20 mmHg PO2) in superfused guinea pig papillary muscles. Simulated ischemia (SI) depolarized the resting membrane by 5 mV and caused a 28% decrease in action potential upstroke (Vmax), a 65% decrease in action potential duration at 90% (APD90), a 40% increase in internal longitudinal resistance (ri), and a 17% decrease in conduction velocity as compared with the 9-K Tyrode control solution. These changes were reversible and reproducible. The decrease in Vmax induced by SI was greater than that associated with a K(+)-induced change in resting membrane potential (RMP). Ryanodine lessened the SI-induced APD90 shortening by 26%, the decrease in Vmax by 42%, the increase in ri by 33%, and the decrease in conduction velocity by 21%. BAY K 8644 did not alter SI-induced APD90 shortening but augmented the decrease in Vmax by 23%, the increase in ri by 67%, and the decrease in conduction velocity by 59%. Neither ryanodine nor BAY K 8644 altered the SI-induced changes in RMP. Our results suggest that changes in intracellular calcium during SI not only influence cellular coupling but also contribute to the apparent non-RMP-dependent component of the change in Vmax and to the change in APD90 induced by SI.
Maruyama
T
T
Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill 27599-7075.
Cascio
W E
WE
Knisley
S B
SB
Buchanan
J
J
Gettes
L S
LS
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D003327:Coronary Disease / Q000503:physiopathology*; D004553:Electric Conductivity; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000187:drug effects / Q000503:physiopathology*; D008564:Membrane Potentials / Q000187:drug effects; D012433:Ryanodine / Q000494:pharmacology*
D012433:Ryanodine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester