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J Appl Physiol 81: 2214-2220, 1996;
8750-7587/96 $5.00
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Journal of Applied Physiology
Vol. 81, No. 5, pp. 2214-2220, November 1996
EXERCISE AND MUSCLE

Effects of DAP on diaphragm force and fatigue, including fatigue due to neurotransmission failure

Erik Van Lunteren and Michelle Moyer

Department of Medicine, Pulmonary Division, Case Western Reserve University and Cleveland Veterans Affairs Medical Center, Cleveland, Ohio 44106

Received 26 December 1995; accepted in final form 29 May 1996.

Van Lunteren, Erik, and Michelle Moyer. Effects of DAP on diaphragm force and fatigue, including fatigue due to neurotransmission failure. J. Appl. Physiol. 81(5): 2214-2220, 1996.---Among the aminopyridines, 3,4-diaminopyridine (DAP) is a more effective K+ channel blocker than is 4-aminopyridine (4-AP), and, furthermore, DAP enhances neuromuscular transmission. Because 4-AP improves muscle contractility, we hypothesized that DAP would also increase force and, in addition, ameliorate fatigue and improve the neurotransmission failure component of fatigue. Rat diaphragm strips were studied in vitro (37°C). In field-stimulated muscle, 0.3 mM DAP significantly increased diaphragm twitch force, prolonged contraction time, and shifted the force-frequency relationship to the left without altering peak tetanic force, resulting in increased force at stimulation frequencies <= 50 Hz. During 20-Hz intermittent stimulation, DAP increased diaphragm peak force compared with control during a 150-s fatigue run and, furthermore, significantly improved maintenance of intratrain force. The relative contribution of neurotransmission failure to fatigue was estimated by comparing the force generated by phrenic nerve-stimulated muscles with that generated by curare-treated field-stimulated muscles. DAP significantly increased force in nerve-stimulated muscles and, in addition, reduced the neurotransmission failure contribution to diaphragm fatigue. Thus DAP increases muscle force at low-to-intermediate stimulation frequencies, improves overall force and intratrain fatigue during 20-Hz intermittent stimulation, and reduces neurotransmission failure.

potassium channel; skeletal muscle; contractility; respiratory muscle; 3,4-diaminopyridine

0161-7567/96 $5.00 Copyright © 1996 the American Physiological Society




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