Calcium handling and action potentials in cardiac myocytes: Biophysical mechanisms

Dr. Vladimir E. Bondarenko

Department of Physiology and Biophysics
School of Medicine and Biomedical Sciences
SUNY at Buffalo, Buffalo, NY 14214

The cardiac action potential (AP) is complex, resulting from the interaction of multiple non-linear time-dependent currents. Mathematical models of the AP have therefore been an important tool in understanding and exploring the biophysical mechanism of AP generation. A mathematical model of the mouse ventricular myocyte action potential has been developed from voltage-clamp data of the underlying currents and calcium transients. The model reproduces the properties of cardiac myocytes from two different regions of the heart: the apex and the septum. The development of Markov models for several of the component currents enables the mouse model to be used to simulate the behavior of genetically modified mice.
To simulate Ca2+ dynamics that include morphological inhomogeneitis, a computer model of graded release of Ca2+ and L-type Ca2+ current inactivation in ferret ventricular myocytes was developed and their role in cardiac cell functioning was investigated. It was found that morphological cellular inhomogeneities created biophysical basis and were responsible for gradness of Ca2+ release in cardiac myocytes. The model successfully reproduced experimental data on Ca2+ dynamics in ferret cardiac myocytes, Ca2+ sparks, and graded Ca2+-induced Ca2+ release.

Recent publications relevant to the talk:
Jiang X., Bett G. C. L., Li X., Bondarenko V. E., and Rasmusson R. L. C-type inactivation involves a significant decrease in the intracellular aqueous pore volume. J. Physiol. (London), 2003, v. 549, n. 3, p. 683-695.
Bondarenko V. E., Chay T. R. Calcium dynamics and generation of propagating waves in a coupled ensemble of neurons with random connection strengths. Int. J. Bifurcat. Chaos, 2003, v.13, n. 6, p. 1509-1527.
Bondarenko V.E., Bett G.C.L., Rasmussson R.L. A model of graded calcium release and L-type Ca2+ channel inactivation in cardiac muscle. Am. J. Physiol., 2004, v.286, n. 3, p. H1154-H1159.
Wang S., Bondarenko V. E., Qu Y., Morales M. J., Rasmusson R. L., Strauss H. C. Activation properties of Kv4.3 channels: Time, voltage and [K+]o dependence. J. Physiol. (London), 2004, v. 557, n. 3, p. 705-717.
Bondarenko V. E., Szigeti G. P., Bett G. C. L., Kim S.-J., Rasmusson R. L. Computer model of action potential of mouse ventricular myocytes. Am. J. Physiol., 2004, v.287, n. 3, p. H1378-H1403.
Zarayskiy V. V., Balasubramanian G., Bondarenko V. E., Morales M. J. Heteropoda toxin 2 is a gating modifier toxin specific for voltage-gated K+ channels of the Kv4 family. Toxicon, 2005, in press.
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