The effects of acidosis on intracellular [Ca²⁺] (Ca_i) have been studied extensively; acidosis increases diastolic Ca_i and the amplitude of the systolic Ca_i transient, although in some studies this is preceded by a small decrease in Ca_i transient amplitude (Orchard and Kentish, 1990). It has been suggested that these changes result from the effects of acidosis on: (i) Ca²⁺ influx via Na/Ca exchange, (ii) release of Ca²⁺ from the sarcoplasmic reticulum and (iii) intracellular Ca²⁺ buffering (Orchard and Kentish, 1990; Orchard, 2004). The relative importance of each of these components is difficult to establish experimentally. We have therefore used a model of the rat ventricular myocyte based on that described by Pandit et al (2001) to investigate whether the integrated response to these changes is compatible with that observed experimentally during acidosis. Figure 1 shows the response of the model to three effects of acidosis suggested by experimental data: (A) Increasing intracellular Na⁺ from 11 mM to 15mM, by increasing background Na⁺ conductance, thus altering Na⁺/Ca²⁺ exchange activity, increased diastolic Ca_i and Ca_i transient amplitude. (B) Decreasing the sensitivity of the ryanodine receptor to trigger Ca²⁺, by decreasing the rate constant for channel opening by a factor of 0.25, decreased Ca_i transient amplitude. (C) Decreasing Ca²⁺ binding to troponin-C, by increasing the off-rate of Ca²⁺ from troponin by a factor of 4.0, decreased diastolic Ca_ibut increased Ca_i transient amplitude. (D) Combining these three changes increased diastolic Ca_i and Ca_i transient amplitude. All changes were made with a time course similar to the change of intracellular pH recorded experimentally; the responses are similar to those recorded experimentally in response to acidosis, consistent with the idea that they underlie the changes of Ca_i observed during acidosis.