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Long-term modulation of Na+ and K+ channels by TGF-β1 in neonatal rat cardiac myocytes

  • Ion Channels, Receptors and Transporters
  • Published:
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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+ (INa) and K+ (IK) currents were investigated under whole-cell patch-clamp conditions. Three K+ currents were isolated: inward rectifier (IKin), outward transitory (Ito), and outward sustained (IKsus). Interestingly, TGF-β1 decreased (50%) the densities of IKin and IKsus but not of Ito. In addition, the growth factor reduced by 80% the amount of INa available at −80 mV. This effect was due to a significant reduction (30%) in the maximum INa recruited at very negative potentials or Imax, as well as to an increased fraction of inactivated Na+ channels. The latter effect was, in turn, associated to a −7 mV shift in V1/2 of inactivation. TGF-β1 also reduced by 60% the maximum amount of intramembrane charge movement of Na+ channels or Qmax, 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 IKsus and IKin. These results may contribute to explaining the previously observed proarrhythmic effects of TGF-β1.

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Acknowledgments

We would like to thank Mario Rodriguez and Esperanza Jimenez for the technical assistance. We also thank Dr. Gary Matthews for his generous gift of anti-pan Na+ channel antibody. This work was supported by a Conacyt grant to GA (56733).

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  1. Department of Biochemistry, Cinvestav-IPN, AP 14-740, Mexico City, DF 07000, Mexico

    Roberto Ramos-Mondragón, Ana Victoria Vega & Guillermo Avila

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  1. Roberto Ramos-Mondragón
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  2. Ana Victoria Vega
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  3. Guillermo Avila
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Correspondence to Guillermo Avila.

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Ramos-Mondragón, R., Vega, A.V. & Avila, G. Long-term modulation of Na+ and K+ channels by TGF-β1 in neonatal rat cardiac myocytes. Pflugers Arch - Eur J Physiol 461, 235–247 (2011). https://doi.org/10.1007/s00424-010-0912-3

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