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Transient outward potassium current, ‘ I to ’, phenotypes in the mammalian left ventricle: underlying molecular, cellular and biophysical mechanisms
Author(s) -
Patel Sangita P.,
Campbell Donald L.
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.086223
Subject(s) - phenotype , electrophysiology , biophysics , cardiac transient outward potassium current , ventricle , protein subunit , microbiology and biotechnology , biology , chemistry , kinetics , patch clamp , biochemistry , neuroscience , medicine , gene , physics , quantum mechanics
At least two functionally distinct transient outward K + current ( I to ) phenotypes can exist across the free wall of the left ventricle (LV). Based upon their voltage‐dependent kinetics of recovery from inactivation, these two phenotypes are designated ‘ I to,fast ’ (recovery time constants on the order of tens of milliseconds) and ‘ I to,slow ’ (recovery time constants on the order of thousands of milliseconds). Depending upon species, either I to,fast , I to,slow or both current phenotypes may be expressed in the LV free wall. The expression gradients of these two I to phenotypes across the LV free wall are typically heterogeneous and, depending upon species, may consist of functional phenotypic gradients of both I to,fast and I to,slow and/or density gradients of either phenotype. We review the present evidence (molecular, biophysical, electrophysiological and pharmacological) for Kv4.2/4.3 α subunits underlying LV I to,fast and Kv1.4 α subunits underlying LV I to,slow and speculate upon the potential roles of each of these currents in determining frequency‐dependent action potential characteristics of LV subepicardial versus subendocardial myocytes in different species. We also review the possible functional implications of (i) ancillary subunits that regulate Kv1.4 and Kv4.2/4.3 (Kvβ subunits, DPPs), (ii) KChIP2 isoforms, (iii) spider toxin‐mediated block of Kv4.2/4.3 ( Heteropoda toxins, phrixotoxins), and (iv) potential mechanisms of modulation of I to,fast and I to,slow by cellular redox state, [Ca 2 + ] i and kinase‐mediated phosphorylation. I to phenotypic activation and state‐dependent gating models and molecular structure–function relationships are also discussed.