Calcium Ion Permeation through the Calcium Release Channel (Ryanodine Receptor) of Cardiac Muscle

Abstract

Single-channel current−voltage (IV) relations were measured from the calcium release channel of cardiac sarcoplasmic reticulum (RyR2) in 21 mixed solutions of 250 mM alkali metal ions (Na+, K+, and Cs+) with sarcoplasmic reticulum lumenal Ca++ ranging from 5 to 50 mM and Mg++ from 1 to 50 mM. The measured IV relations were analyzed by the extended Poisson−Nernst−Planck (PNP) formulation (Chen, D. P.; Xu, L.; Tripathy, A.; Meissner, G.; Eisenberg, B. Biophys. J. 1999, 76, 1346) to give the permeation properties of Ca++ and Mg++. The results indicate that applying PNP theory, two adjustable parameters (diffusion coefficient (D) and “excess” chemical potentials (μ̄)) suffice to predict the flow of Ca++ from the sarcoplasmic reticulum in cardiac muscle. The fitting parameters for Ca++ and Mg++ are D(Ca) = 8.4 ± 0.7 × 10-8 cm2/s, μ̄(Ca) = −91 ± 6 mV and D(Mg) = 5.4 ± 0.7 × 10-8 cm2/s and μ̄(Mg) = −53 ± 6 mV. The data are used to predict the calcium ion activity profiles in the RyR2 pore, the calcium ion fluxes in solutions of physiological interest, and the competitive permeation of Ca++ and Mg++.