Effect of k+ channel blockade on fatigue in rat diaphragm
muscle.
Lunteren, Erik Van, Michelle Moyer, and Augusto Torres.
Department of Medicine, Pulmonary Division, Case Western Reserve
University and Cleveland VA Medical Center, Cleveland, OH 44106
APStracts 2:0228A, 1995.
K+ channel blockers increase skeletal muscle force during twitch
contractions; the present study determined whether K+ channel
blockade also modulates force during longer term and higher frequency
stimulation. 4-Aminopyridine (4-AP, 0.3 mM) increased rat diaphragm
force during twitch, 5 Hz and 20 Hz, but not 100 Hz, stimulation, and
prolonged isometric contraction but not half-relaxation time. In
response to continuous 5 Hz stimulation, the rate of force decline
was accelerated by 4-AP, so that over time force dropped below that
of control muscle strips. In response to intermittent 20 Hz
stimulation, 4-AP produced an early force potentiation; the 4-AP
induced force increase was maintained throughout repetitive
stimulation, despite an accelerated rate of force decline. In
response to continuous 100 Hz stimulation, 4-AP did not affect rate
of force decline. During 5 and 20 Hz stimulation, there was an
interaction between 4-AP and duration of stimulation in prolonging
contraction and especially half-relaxation time. Tetraethylammonium
(10 mM) augmented diaphragm force less than did 4-AP, did not affect
rate of force decline during 5 Hz stimulation, and did not interact
with fatigue to prolong isometric twitch kinetics. These data
indicate that K+ channel blockade with 4-AP increases diaphragm force
at low to intermediate stimulation frequencies, may increase early
force potentiation during repetitive contraction, and depending on
stimulation pattern either accelerates or has no effect on rate of
fatigue.
Received 3 October 1994; accepted in final form 21 February 1995.
APS Manuscript Number A1021-4.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 May 1995.