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Oestrogen directly inhibits the cardiovascular L-type Ca2+ channel Cav1.2

Nina D Ullrich1, Alexandra Koschak, Kenneth T MacLeod

  • 1Imperial College London, Cardiac Medicine, NHLI London, UK. ullrich@pyl.unibe.ch

Biochemical and Biophysical Research Communications
|July 31, 2007
PubMed

Insights

Oestrogen directly inhibits the cardiovascular L-type calcium current (I(CaL)) by interacting with the Ca(v)1.2 channel protein. This action reduces heart muscle contraction and impacts coronary blood flow.

Area of Science:

  • Cardiovascular Physiology
  • Endocrinology
  • Molecular Pharmacology

Background:

  • Oestrogen influences vascular smooth muscle and cardiomyocyte function.
  • Negative inotropic effects of oestrogen on the heart are linked to L-type Ca(2+) channel (Ca(v)1.2) inhibition.
  • Mechanisms of oestrogen-mediated Ca(v)1.2 channel modulation are not fully understood.

Purpose of the Study:

  • To test the hypothesis that oestrogen directly inhibits the cardiovascular L-type calcium current (I(CaL)).
  • To investigate the direct interaction between oestrogen and the Ca(v)1.2 channel.

Main Methods:

  • Whole-cell patch-clamp technique applied to Ca(v)1.2-transfected HEK-293 cells.
  • Measurement of I(CaL) in the presence of varying oestrogen concentrations.
  • Analysis of voltage-dependent activation, inactivation, and block characteristics.

Main Results:

  • Oestrogen (50 microM) significantly reduced I(CaL) by 50%.
  • Oestrogen shifted voltage-dependent activation and availability of Ca(v)1.2 channels to more negative potentials.
  • Oestrogen exhibited rate-dependent block of the Ca(2+) channel, with increased efficiency at higher stimulation frequencies.

Conclusions:

  • Oestrogen directly inhibits I(CaL) through interaction with the Ca(v)1.2 channel protein.
  • This direct inhibition provides a mechanism for oestrogen's effects on cardiac and vascular contractility.
  • Oestrogen's modulatory effects on Ca(v)1.2 channels are frequency-dependent.

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