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The guinea-pig ventricular cell model, originally developed by Noble et al in 1991, has been greatly extended to include accumulation and depletion of calcium in a diadic space between the sarcolemma and the sarcoplasmic reticulum where, according to contempory understanding, the majority of calcium-induced calcium release is triggered. The calcium in this(More)
Late sodium current in cardiac cells is very small compared with the fast component, but as it flows throughout the action potential it may make a substantial contribution to sodium loading during each cardiac cycle. Late sodium current may contribute to triggering arrhythmia in two ways: by causing repolarisation failure (early after depolarisations); and(More)
The experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. In this article we introduce a mathematical model of the action potential of human ventricular cells that, while including a high level(More)
Early development of ionic models for cardiac myocytes, from the pioneering modification of the Hodgkin-Huxley giant squid axon model by Noble to the iconic DiFrancesco-Noble model integrating voltage-gated ionic currents, ion pumps and exchangers, Ca(2+) sequestration and Ca(2+)-induced Ca(2+) release, provided a general description for a mammalian(More)
OBJECTIVE The L-type Ca(2+) current (I(Ca,L)) contributes to the generation and modulation of the pacemaker action potential (AP). We investigated facilitation of I(Ca,L) in sino-atrial cells. METHODS Facilitation was studied in regularly-beating cells isolated enzymatically from young albino rabbits (0.8-1 kg). We used the whole-cell patch-clamp(More)
The role of the Na+/Ca2+ exchanger (NCX) as the main pathway for Ca2+ extrusion from ventricular myocytes is well established. However, both the role of the Ca2+ entry mode of NCX in regulating local Ca2+ dynamics and the role of the Ca2+ exit mode during the majority of the physiological action potential (AP) are subjects of controversy. The functional(More)
BACKGROUND Activation of the gastrin-cholecystokinin(B) (CCK(B)) receptor stimulates cell proliferation and increases production of ligands for the epidermal growth factor receptor (EGF-R). AIMS To determine the role of gastrin-CCK(B) activation in stimulation of cell proliferation via paracrine activation of EGF-R. METHODS AGS cells were transfected(More)
A decrease of the transient outward potassium current (Ito) has been observed in cardiac hypertrophy and contributes to the altered shape of the action potential (AP) of hypertrophied ventricular myocytes. Since the shape and duration of the ventricular AP are important determinants of the Ca2+ influx during the AP (QCa), we investigated the effect of(More)
Epithelial organization is maintained by cell proliferation, migration, and differentiation. In the case of the gastric epithelium, at least some of these events are regulated by the hormone gastrin. In addition, gastric epithelial cells are organized into characteristic tubular structures (the gastric glands), but the cellular mechanisms regulating the(More)
Co-localization of Na+/Ca2+ exchangers (NCX) with ryanodine receptors (RyRs) is debated. We incorporate local NCX current in a biophysically detailed model of L-type Ca2+ channels (LCCs) and RyRs and study the effect of NCX on the regulation of Ca2+-induced Ca2+ release and the shape of the action potential. In canine ventricular cells, under pathological(More)