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TOPICAL REVIEWS |
1 Department of Physiology and Biophysics, University at Buffalo, State University of New York, Buffalo, NY 14214, USA
At least two functionally distinct transient outward K+ current (Ito) 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 ‘Ito,fast’ (recovery time constants on the order of tens of milliseconds) and ‘Ito,slow’ (recovery time constants on the order of thousands of milliseconds). Depending upon species, either Ito,fast, Ito,slow or both current phenotypes may be expressed in the LV free wall. The expression gradients of these two Ito phenotypes across the LV free wall are typically heterogeneous and, depending upon species, may consist of functional phenotypic gradients of both Ito,fast and Ito,slow and/or density gradients of either phenotype. We review the present evidence (molecular, biophysical, electrophysiological and pharmacological) for Kv4.2/4.3 
subunits underlying LV Ito,fast and Kv1.4 subunits underlying LV Ito,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 (Kvß 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 Ito,fast and Ito,slow by cellular redox state, [Ca2+]i and kinase-mediated phosphorylation. Ito phenotypic activation and state-dependent gating models and molecular structure–function relationships are also discussed.
(Received 7 March 2005;
accepted after revision 13 April 2005;
first published online 14 April 2005)
Corresponding author D. L. Campbell: University at Buffalo, SUNY, Department of Physiology and Biophysics, 124 Sherman Hall, Buffalo, NY 14214-3078, USA. Email: dc25{at}buffalo.edu
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