When cardiac muscle is exposed to an acid solution, the strength of contraction decreases rapidly. This is due predominantly to an acidosis-induced decrease in myofilament Ca sensitivity, modulated by changes in Ca handling that also slow the decline of the Ca transient (Orchard, 1987). Despite a maintained intracellular acidosis, the decrease of contraction is followed by a slower recovery, which is accompanied by an increase in Ca transient amplitude and recovery of its time course (Orchard, 1987). The recovery of contraction appears to be due to an increase in sarcoplasmic reticulum (SR) Ca content as a result of: (i) desensitisation of the ryanodine receptor to trigger Ca. The subsequent decrease in Ca transient amplitude increases Ca influx via the Ca current, and decreases Ca efflux via Na-Ca exchange. In the absence of other changes this increases cellular, including SR, Ca content, and hence Ca release, until the amplitude of the Ca transient recovers to control levels. This is, however, achieved at a higher SR Ca content and smaller fractional release than previously (Choi et al. 2000). (ii) Activation of acid extrusion pathways, which increases intracellular [Na] and hence, via Na-Ca exchange, intracellular Ca (Bountra & Vaughan-Jones, 1989). (iii) Altered phosphorylation of the regulatory protein phospholamban (PLB), which causes PLB to unbind from the SR Ca pump, increasing its activity and SR Ca uptake (DeSantiago et al. 2004). Despite these marked effects on excitation-contraction coupling, reducing extracellular pH from 7.4 to 6.5 has relatively modest effects on the electrical activity of atrial and ventricular myocytes isolated from rat heart when the perforated patch clamp technique is used to minimise disturbance of the intracellular milieu (Komukai et al. 2002). However ecg measurements in isolated rat heart show that acidosis markedly slows heart rate and increases the P-R interval, suggesting that the sino-atrial and atrio-ventricular nodes are particularly sensitive to pH. This has been investigated further using the optical dye RH237 to monitor electrical activity on the epicardial surface of isolated rabbit hearts. This revealed that perfusion with acidic solution (pH 6.8) caused a significant delay in the time between atrial activation and the appearance of electrical activity on the ventricular epicardial surface. The conclusion that delayed conduction at the a-v node underlies this result is supported by two further observations: (i) ventricular conduction velocity was not significantly slower; depressed ventricular conduction only became evident at pH 6.3; (ii) experiments on isolated a-v nodal preparations confirmed that the time for atrial-bundle of His (A-H) conduction is slowed by ~20% at pH 6.8. Further slowing of A-H conduction occurs at pH 6.3 to the extent that complete block is frequently observed. Thus it appears that moderate acidosis (pH 6.8) affects cardiac electrophysiological function primarily by altering the electrical activity of nodal tissue. At more acidic pH values (6.3) myocardial conduction velocity is depressed and a-v nodal conduction is dramatically prolonged.