Journal of Applied Physiology, Vol 71, Issue 3 841-846, Copyright © 1991 by American Physiological Society
Multiple effects of BAY K 8644 and nifedipine on isolated diaphragmatic fibers in vitro
N. Viires, D. Pavlovic and M. Aubier
Laboratoire de Pathologie Experimentale, Institut National de la Sante et de la Recherche, Medicale U 226, Faculte Xavier Bichat, Paris, France.
The dose-response effects of BAY K 8644 and nifedipine on diaphragmatic
contractility were assessed in vitro. Isolated diaphragmatic fibers were
obtained from rats and placed in an open-topped channel of a Plexiglas
tissue chamber perfused with continuously flowing Krebs solution heated to
37 degrees C. Isometric twitch force, generated in response to 1-Hz
supramaximal electrical stimulation (4 times/min), was measured with a
highly sensitive photoelectric force transducer. Low doses of BAY K 8644 or
nifedipine (10(-7) M) were without effect on twitch tension. For 10(-6) M,
twitch tension increased by 10 +/- 1% (P less than 0.005) for both drugs.
For 10(-5) M, twitch tension increased by 12 +/- 1% (P less than 0.05), and
maximal contractures were observed (BAY K 8644 and nifedipine).
Simultaneous drug administration did not reveal mutual antagonism as
expected; instead the effects were additive, with twitch tension increasing
by 30 +/- 2% (P less than 0.001) for 10(-5) M BAY K 8644 + nifedipine. Both
BAY K 8644 and nifedipine altered twitch characteristics. In low-calcium
media (0.5 mM) twitch potentiation produced by the two drugs was further
enhanced (increasing 60% for 10(-5) M BAY K 8644 or nifedipine).
Contractures, by contrast, were abolished. From these results it is
difficult to reconcile a unique action of these drugs on calcium channels
as is conventionally accepted.
