Role of individual ionic current systems in ventricular cells hypothesized by a model study.
Individual ion channels or exchangers are described with a common set of equations for both the sinoatrial node pacemaker and ventricular cells. New experimental data are included, such as the new kinetics of the inward rectifier K+ channel, delayed rectifier K+ channel, and sustained inward current. The gating model of Shirokov et al. (J Gen Physiol 102: 1005-1030, 1993) is used for both the fast Na+ and L-type Ca2+ channels. When combined with a contraction model (Negroni and Lascano: J Mol Cell Cardiol 28: 915-929, 1996), the experimental staircase phenomenon of contraction is reconstructed. The modulation of the action potential by varying the external Ca2+ and K+ concentrations is well simulated. The conductance of I(CaL) dominates membrane conductance during the action potential so that an artificial increase of I(to), I(Kr), I(Ks), or I(KATP) magnifies I(CaL) amplitude. Repolarizing current is provided sequentially by I(Ks), I(Kr), and I(K1). Depression of ATP production results in the shortening of action potential through the activation of I(KATP). The ratio of Ca2+ released from SR over Ca2+ entering via I(CaL) (Ca2+ gain = approximately 15) in excitation-contraction coupling well agrees with the experimental data. The model serves as a predictive tool in generating testable hypotheses.
Matsuoka
Satoshi
S
Department of Physiology and Biophysics, Kyoto University Graduate School of Medicine, Yoshidakonoe-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Sarai
Nobuaki
N
Kuratomi
Shinobu
S
Ono
Kyoichi
K
Noma
Akinori
A
D000200:Action Potentials / Q000502:physiology; D000465:Algorithms; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000502:physiology; D048429:Cell Size / Q000502:physiology; D003198:Computer Simulation; D003600:Cytosol / Q000737:chemistry; D004558:Electric Stimulation; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000166:cytology; D007473:Ion Channels / Q000502:physiology*; D017136:Ion Transport / Q000502:physiology; D007477:Ions / Q000032:analysis / Q000378:metabolism; D007700:Kinetics; D008564:Membrane Potentials / Q000502:physiology; D008954:Models, Biological; D032383:Myocytes, Cardiac / Q000502:physiology; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D019837:Ryanodine Receptor Calcium Release Channel / Q000502:physiology; D012508:Sarcolemma / Q000502:physiology; D012518:Sarcomeres / Q000502:physiology; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000502:physiology; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D016276:Ventricular Function
D002135:Calcium-Binding Proteins; D007473:Ion Channels; D007477:Ions; D019837:Ryanodine Receptor Calcium Release Channel; D019831:Sodium-Calcium Exchanger; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D002118:Calcium