Figure 4.

Possible mechanisms for the increase in diastolic intracellular Ca2+ concentration ([Ca2+]i) with increased stimulation rate. Two mechanisms are shown. (1) The increase in rate increases Ca²⁺ influx per unit time and decreases the time over which efflux can occur resulting in influx becoming greater than efflux. This increases diastolic [Ca²⁺]_i and thence average [Ca²⁺]_i. Via sodium-calcium exchange (NCX), this elevation of average [Ca²⁺]_i increases Ca²⁺ efflux to equal the influx so that influx and efflux are again equal. (2) Increased rate elevates intracellular Na⁺ concentration ([Na⁺]_i), which decreases Ca²⁺ efflux on NCX. Therefore, a greater increase in average [Ca²⁺]_i is required to maintain Ca²⁺ efflux equal to influx.