We examined the effect of shrinkage on Na+-H+ exchange in single muscle fibers at intracellular pH (pH(i)) values of 6.8, 7.2, and 7.6 using pH microelectrodes and internal dialysis. Under normotonic conditions (975 mosmol/ kgH(2)O) at pH(i) 6.8, the amiloride-sensitive acid-extrusion rate (J(Amil/S)) averaged 17 mu M/min. Exposure to hypertonic solutions (1,600 mosmol/kgH(2)O) increased J(Amil/S) to 304 mu M/min at pH(i) 6.8. At pH(i) similar to 7.2 and 7.6, hypertonicity increased J(Amil/S) from similar to 0 to similar to 172 mu M/min (pH(i) 7.2) and similar to 0 to similar to 90 mu M/min (pi-ii 7.6). Thus, under normotonic conditions, Nat-HC exchange activity is slight at pH(i) similar to 6.8 and virtually nil at higher pH(i) values. Shrinkage stimulated Na+-H+ exchange, more at low pH(i) values. We also examined the Cl- dependence of the Na+-H+ exchanger's response to shrinkage. Our results indicate that shrinkage-induced activation of Na+-H+ exchange requires Cl-, specifically intracellular Cl-. These results establish that shrinkage is both pH(i) dependent and requires intracellular Cl-.
