title: Long-term modulation of Na+ and K+ channels by TGF-β1 in neonatal rat cardiac myocytes.
abstract: Previous work shows that transforming growth factor-β1 (TGF-β1) promotes several heart alterations, including atrial fibrillation (AF). In this work, we hypothesized that these effects might be associated with a potential modulation of Na(+) and K(+) channels. Atrial myocytes were cultured 1-2 days under either control conditions, or the presence of TGF-β1. Subsequently, Na(+) (I(Na)) and K(+) (I(K)) currents were investigated under whole-cell patch-clamp conditions. Three K(+) currents were isolated: inward rectifier (I(Kin)), outward transitory (I(to)), and outward sustained (I(Ksus)). Interestingly, TGF-β1 decreased (50%) the densities of I(Kin) and I(Ksus) but not of I(to). In addition, the growth factor reduced by 80% the amount of I(Na) available at -80 mV. This effect was due to a significant reduction (30%) in the maximum I(Na) recruited at very negative potentials or I(max), as well as to an increased fraction of inactivated Na(+) channels. The latter effect was, in turn, associated to a -7 mV shift in V(1/2) of inactivation. TGF-β1 also reduced by 60% the maximum amount of intramembrane charge movement of Na(+) channels or Q(max), but did not affect the corresponding voltage dependence of activation. This suggests that TGF-β1 promotes loss of Na(+) channels from the plasma membrane. Moreover, TGF-β1 also reduced (50%) the expression of the principal subunit of Na(+) channels, as indicated by western blot analysis. Thus, TGF-β1 inhibits the expression of Na(+) channels, as well as the activity of K(+) channels that give rise to I(Ksus) and I(Kin). These results may contribute to explaining the previously observed proarrhythmic effects of TGF-β1.
authors.affiliation: Department of Biochemistry, Cinvestav-IPN, AP 14-740, Mexico City, DF 07000, Mexico.
authors.forename: Roberto
authors.initials: R
authors.lastname: Ramos-Mondragón
authors.forename: Ana Victoria
authors.initials: AV
authors.lastname: Vega
authors.forename: Guillermo
authors.initials: G
authors.lastname: Avila
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015640:Ion Channel Gating / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D062554:NAV1.5 Voltage-Gated Sodium Channel; D015221:Potassium Channels; C568322:Scn5a protein, rat; D015222:Sodium Channels; D053773:Transforming Growth Factor beta1