Acidosis and electrical signaling. Changes in pH_i, [H⁺]_i, and AP induced by extracellular, intracellular, and combined acidosis (see cartoon insets) in rabbit myocytes (A; i). A reduction in pH_o from 7.4 to 6.5 for 2 min elicited only a small drop in pH_i. (ii) Extracellular acidosis (2 min; red) shortened APD and depressed the plateau (APD₉₀, control = 336 ± 33 msec and low pH_o = 279 ± 31 msec; n = 9; P < 0.01, paired). (B; i) In contrast, exposure to 80.0 mM acetate, pH_o 7.4, induced a rapid sustained fall in pH_i. (ii) Intracellular acidosis (2 min; red) prolonged APD, slowed phase 1 repolarization, and elevated the plateau (APD₉₀, control = 324 ± 29 msec and low pH_i = 491 ± 31 msec; n = 15; P < 0.01, paired). (C; i) Combined acidosis (2 min; red) involved reducing pH_o from 7.4 to 6.5 in the presence of 30 mM acetate. pH_i fell by approximately the same extent as with intracellular acidosis alone (B). (ii) Combined acidosis elicited changes in the AP that were similar to those during intracellular acidosis (APD₉₀, control = 343 ± 24 and combined acidosis = 481 ± 30 msec; n = 6; P < 0.01, paired). The control values of pH_i for each type of acidosis were very similar: extracellular acidosis, 7.18 ± 0.05 (n = 7); intracellular acidosis, 7.22 ± 0.02 (n = 17); and combined acidosis, 7.16 ± 0.04 (n = 7).