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Endothelin activates voltage-dependent Ca2+ current by a G protein-dependent mechanism in rabbit cardiac myocytes.

Publication ,  Journal Article
Lauer, MR; Gunn, MD; Clusin, WT
Published in: J Physiol
March 1992

1. Endothelin is a vasoactive peptide released from vascular endothelial cells which has potent cardiac inotropic effects. We examined the effect of endothelin on the verapamil-sensitive Ca2+ current (ICa) in enzymatically dispersed rabbit ventricular myocytes. 2. Using the whole-cell voltage clamp technique with a standard dialysing pipette solution, the application of extracellular endothelin (20 nM) did not increase the peak ICa, but in fact caused a small reversible decline (903 +/- 109 pA without endothelin, 727 +/- 95 pA with endothelin (means +/- S.E.M., n = 14, P less than 0.05)). 3. If GTP (100 microM) was added to the pipette solution, the extracellular application of endothelin (0.2 or 20 nM) caused a large, reproducible increase in peak ICa (871 +/- 85 pA without endothelin, 1230 +/- 110 pA with 20 nM-endothelin (n = 10, P less than 0.05). The endothelin enhancement of ICa occurred after a delay of approximately 3-4 min at room temperature. 4. The GTP requirement for the endothelin effect on ICa suggests that its effect may be mediated through a G protein-dependent pathway. To investigate this further, experiments were performed with pipette solutions containing guanosine-5'-O-(2-thiodiphosphate) (GDP beta S), a GDP analogue which inhibits G protein cycling. With the addition of GDP beta S (0.5-5.0 mM) to the pipette solution (along with 100 microM-GTP), the effect of endothelin on peak ICa was blocked (1062 +/- 86 pA without endothelin, 1170 +/- 134 pA with endothelin (n = 11, P greater than 0.05)). 5. Incubation of myocytes with pertussis toxin (500 ng/ml) prevented the partial ACh-induced reversal of the isoprenolol enhancement of ICa. However, this identical treatment failed to block the endothelin enhancement of the voltage-dependent Ca2+ current (n = 4). 6. Taken together, these results confirm that while the effect of endothelin in rabbit cardiac ventricular myocytes is mediated through a G protein-dependent pathway, the G protein involved is pertussis toxin-insensitive.

Duke Scholars

Published In

J Physiol

DOI

ISSN

0022-3751

Publication Date

March 1992

Volume

448

Start / End Page

729 / 747

Location

England

Related Subject Headings

  • Virulence Factors, Bordetella
  • Time Factors
  • Thionucleotides
  • Rabbits
  • Physiology
  • Pertussis Toxin
  • Myocardium
  • Membrane Potentials
  • Isoproterenol
  • In Vitro Techniques
 

Citation

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Lauer, M. R., Gunn, M. D., & Clusin, W. T. (1992). Endothelin activates voltage-dependent Ca2+ current by a G protein-dependent mechanism in rabbit cardiac myocytes. J Physiol, 448, 729–747. https://doi.org/10.1113/jphysiol.1992.sp019067
Lauer, M. R., M. D. Gunn, and W. T. Clusin. “Endothelin activates voltage-dependent Ca2+ current by a G protein-dependent mechanism in rabbit cardiac myocytes.J Physiol 448 (March 1992): 729–47. https://doi.org/10.1113/jphysiol.1992.sp019067.
Lauer, M. R., et al. “Endothelin activates voltage-dependent Ca2+ current by a G protein-dependent mechanism in rabbit cardiac myocytes.J Physiol, vol. 448, Mar. 1992, pp. 729–47. Pubmed, doi:10.1113/jphysiol.1992.sp019067.
Journal cover image

Published In

J Physiol

DOI

ISSN

0022-3751

Publication Date

March 1992

Volume

448

Start / End Page

729 / 747

Location

England

Related Subject Headings

  • Virulence Factors, Bordetella
  • Time Factors
  • Thionucleotides
  • Rabbits
  • Physiology
  • Pertussis Toxin
  • Myocardium
  • Membrane Potentials
  • Isoproterenol
  • In Vitro Techniques