FIG. 3.

Intracellular electrolyte homeostasis in the setting of altered Na⁺/K⁺ pump activity/turnover rate due to a step change in temperature (23–37°C). As noted, the electrogenic Na⁺/K⁺ pump current is changed significantly when intracellular and extracellular ion concentrations are altered to reflect the ionic milieu of the chondrocyte matrix found in vivo (shown in inset, A); compare to simulations performed assuming a baseline synovial fluid environment (Fig. 1D). In (A) we illustrate steady-state voltage dependence and the temperature dependence of the Na⁺/K⁺ pump current. The steady-state current at 23°C (black trace), as well as at 37°C (red trace), is shown. The additional Na⁺/K⁺ pump current simulated at a pathophysiological temperature hyperpolarizes the chondrocyte resting membrane potential by ∼25 mV at 37°C in the chondrocyte milieu. (B) Also shows the time-dependent hyperpolarization of chondrocyte membrane potential resulting from a step change in temperature from 23°C to 37°C, as well as the corresponding alterations in intracellular Na⁺, K⁺, and Ca²⁺. In the cases of Na⁺ and K⁺ these changes are small: the shift in, for example, [Na⁺]_i is about a 20% change over the time course measured and likely to be of small physiological relevance overall. The intracellular Ca²⁺ level changes transiently (perhaps due to the intrinsic voltage dependence of the Na⁺/Ca²⁺ exchanger or specific model-dependent features of intracellular Ca²⁺ buffering) but quickly stabilizes near 0.2 μM, an accepted level for a resting mammalian cell.