Van Lunteren E, Moyer M
Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
J Appl Physiol (1985). 1996 Nov;81(5):2214-20. doi: 10.1152/jappl.1996.81.5.2214.
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 degrees 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 < or = 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.
在氨基吡啶类药物中，3,4 - 二氨基吡啶（DAP）是一种比4 - 氨基吡啶（4 - AP）更有效的钾通道阻滞剂，此外，DAP还能增强神经肌肉传递。由于4 - AP可改善肌肉收缩力，我们推测DAP也会增加肌力，并且还能减轻疲劳并改善疲劳中的神经传递衰竭成分。对大鼠膈肌条进行体外研究（37℃）。在电场刺激的肌肉中，0.3 mM DAP可显著增加膈肌抽搐力，延长收缩时间，并使力 - 频率关系向左移位，而不改变强直收缩峰值力，从而在刺激频率≤50 Hz时增加肌力。在20 Hz间歇性刺激期间，与对照相比，DAP在150秒疲劳试验期间增加了膈肌峰值力，此外，还显著改善了每次训练期间肌力的维持。通过比较膈神经刺激肌肉产生的力与箭毒处理的电场刺激肌肉产生的力，评估神经传递衰竭对疲劳的相对贡献。DAP显著增加了神经刺激肌肉的肌力，此外，还减少了神经传递衰竭对膈肌疲劳的影响。因此，DAP在低至中等刺激频率下增加肌肉力量，在20 Hz间歇性刺激期间改善整体力量和每次训练期间的疲劳，并减少神经传递衰竭。
