tailieunhanh - Báo cáo y học: " Modeling CICR in rat ventricular myocytes: voltage clamp studies"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học quốc tế cung cấp cho các bạn kiến thức về ngành y đề tài: Modeling CICR in rat ventricular myocytes: voltage clamp studies | Krishna et al. Theoretical Biology and Medical Modelling 2010 7 43 http content 7 1 43 RESEARCH THEORETICAL BIOLOGY AND MEDICAL MODELLING Open Access Modeling CICR in rat ventricular myocytes voltage clamp studies 12 3 4 1 Abhilash Krishna Liang Sun Miguel Valderrábano Philip T Palade John W Clark Jr Correspondence j wc@ department of Electricaland Computer Engineering Rice University 6100 Main Street Houston 77005 USA Abstract Background The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release CICR in cardiac myocytes with voltage clamp VC studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2 loading of the sarcoplasmic reticulum SR and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2 release. Here we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2 concentration Ca2 myo . Methods The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments cell cytosol SR and the dyadic coupling unit DCU in which resides the mechanistic basis of CICR . The DCU is described as a controller-actuator mechanism internally stabilized by negative feedback control of the unit s two diametrically-opposed Ca2 channels triggerchannel and release-channel . It releases Ca2 flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump regulating Ca2 myo. .