Evidence for an extracellular mechanism for the action of H+ on recovery of muscles following fatigue.

Isolated rat diaphragm strips were fatigued by repetitive trains of tetanic stimulation for 3 min. Maximum isometric tension fell to approximately 20% of the normal level. Tension recovered to the prefatigue level a few minutes after the fatiguing stimulation stopped. In normal, bicarbonate-buffered Tyrode solution at pH 7.4, the half recovery time (t1/2) is typically 1-2 min. This is not significantly changed by presoaking in Tyrode at low pH (6.2), amiloride (10(-4) M), which blocks H+--Na+ exchange, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid (10(-4) M), which blocks HCO-3--Cl- exchange, or a combination of these treatments. When the extracellular pH is low (pH 6.2) during recovery the recovery rate falls to approximately 10% of its normal level (t1/2 = 15 min). In the absence of external bicarbonate, using morpholinopropanesulfonic acid buffers, recovery can still be rapid (t1/2 = 2.6 min) if the pH is high but is very slow (t1/2 = 30 min) at pH 6.25. Sites on the external muscle fibre surface thus appear to influence the recovery process. These sites are pH dependent in the range of pH 6.2--7.4 which suggests that they contain a chemical group with a pK in this range.