Modeling the Effect of Kv1.5 Block on the Canine Action Potential
Autor: | Joachim Almquist, Ingemar Jacobson, Mikael Wallman, Mats Jirstrand |
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Přispěvatelé: | Publica |
Rok vydání: | 2010 |
Předmět: |
Atrial action potential
Markov chain Chemistry Models Cardiovascular Prolongation Block (permutation group theory) Biophysics Action Potentials In Vitro Techniques Pharmacology Markov model Models Biological Biophysical Phenomena Markov Chains Biological Systems and Multicellular Dynamics Kv1.5 Potassium Channel Electrophysiology Dogs Potassium Channel Blockers Animals Repolarization Myocytes Cardiac Heart Atria Neuroscience Ion channel |
Zdroj: | Biophysical Journal. 99(9):2726-2736 |
ISSN: | 0006-3495 |
DOI: | 10.1016/j.bpj.2010.08.062 |
Popis: | A wide range of ion channels have been considered as potential targets for pharmacological treatment of atrial fibrillation. The Kv1.5 channel, carrying the IKur current, has received special attention because it contributes to repolarization in the atria but is absent or weakly expressed in ventricular tissue. The dog serves as an important animal model for electrophysiological studies of the heart and mathematical models of the canine atrial action potential (CAAP) have been developed to study the interplay between ionic currents. To enable more-realistic studies on the effects of Kv1.5 blockers on the CAAP in silico, two continuous-time Markov models of the guarded receptor type were formulated for Kv1.5 and subsequently inserted into the Ramirez-Nattel-Courtemanche model of the CAAP. The main findings were: 1), time- and state-dependent Markov models of open-channel Kv1.5 block gave significantly different results compared to a time- and state-independent model with a downscaled conductance; 2), the outcome of Kv1.5 block on the macroscopic system variable APD90 was dependent on the precise mechanism of block; and 3), open-channel block produced a reverse use-dependent prolongation of APD90. This study suggests that more-complex ion-channel models are a prerequisite for quantitative modeling of drug effects. |
Databáze: | OpenAIRE |
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