Transient outward potassium current, 'Ito', phenotypes in the mammalian left ventricle: underlying molecular, cellular and biophysical mechanisms.

摘要: At least two functionally distinct transient outward K+ current (Ito) phenotypes can exist across the free wall of left ventricle (LV). Based upon their voltage-dependent kinetics recovery from inactivation, these are designated ‘Ito,fast’ (recovery time constants on order tens milliseconds) and ‘Ito,slow’ thousands milliseconds). Depending species, either Ito,fast, Ito,slow or both may be expressed in LV wall. The expression gradients Ito typically heterogeneous and, depending consist functional phenotypic Ito,fast and/or density phenotype. We review present evidence (molecular, biophysical, electrophysiological pharmacological) for Kv4.2/4.3 α subunits underlying Kv1.4 speculate potential roles each currents determining frequency-dependent action characteristics subepicardial versus subendocardial myocytes different species. also possible implications (i) ancillary that regulate (Kvβ subunits, DPPs), (ii) KChIP2 isoforms, (iii) spider toxin-mediated block (Heteropoda toxins, phrixotoxins), (iv) mechanisms modulation by cellular redox state, [Ca2+]i kinase-mediated phosphorylation. activation state-dependent gating models molecular structure–function relationships discussed.