A model of sarcolemmal calcium(2+) currents and cytosolic calcium(2+) transients in a rat ventricular cell
Clark, John W., Jr.
Master of Science
We have developed a mathematical model of the L-type Ca2+ current and cytosolic Ca2+ transient, which is based on data from whole-cell voltage clamp experiments on rat ventricular myocytes. Modified Goldman-Hodgkin-Katz (GHK) equations are provided to account for the different ion selectivity of the DHP-sensitive Ca2+ current channel. The decay of whole cell currents obtained by maintained depolarization is characterized by means of voltage and Ca2+-dependent inactivation embedded in a 5-state dynamic DHP channel model. To characterize a reduced amount of steady-state inactivation of DHP channel in the presence of [Ca 2+]o, a mechanism is used in the model whereby Ca 2+ also inhibits the voltage-dependent inactivation pathway. The 5-state DHP model is also used to simulate single-channel activity. Cytosolic Ca 2+ transients are studied as well. They derive mainly from secondary Calcium-Induced-Calcium-Release (CICR) from the Sarcoplasmic Reticulum (SR). We have developed a 4-state RyR-sensitive Ca2+ model that describes the kinetics of the release channel. This model provides close fitting of cytosolic Ca2+-transient data and mimics the high gain, graded Ca2+ release behavior of the channel. Overall, the model provides a quantitative description of the Ca2+ subsystem in the mammalian heart.
Biomedical engineering; Biophysics