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Altered cardiac chronotropic responses in βARK 2 knockout mice

Publication ,  Journal Article
Walker, JKL; Peppel, K; Lefkowitz, RJ; Caron, MG; Fisher, JT
Published in: FASEB Journal
1998

G protein-coupled receptor kinases (GRKs) desensitize agonist-activated G protein-coupled receptors (GPCRs) thus attenuating their responses. In cell culture experiments, GRK 3 (βARK 2) phosphorylates and desensitizes multiple GPCRs, including muscarinic acetylcholine receptors (mAChR). Genetically altered mice, lacking βARK 2 (βARK 2 -/-), display a more rapid heart rate recovery after an i.v. injection of methacholine, than wildtype mice (WT). Since this observation is contrary to that expected (assuming βARK 2 desensitizes cardiac m2AChR in vivo) and given that i.v. methacholine induces hypotension, we hypothesized that BARK 2 may desensitize a central component of cardiovascular control, the baroreceptor reflex. To test this hypothesis we examined baroreflexes as well as the impact of direct cardiac m2AChR activation with vagal stimulation. During vagal nerve stimulation (10, 15 and 20 Hz) heart rate decreased, and recovered, similarly in βARK 2 -/- and WT mice. However, the increase in heart rate associated with sodium nitroprusside-induced hypotension was significantly greater in βARK 2 -/- (88 ± 12 beats/min) than WT (31 ± 16 beats/min) mice. Interestingly, propranolol significantly decreased resting heart rate in WT (486 ± 28 to 419 ± 22 beats/min), but not βARK 2 -/-mice (443 ±26 to 426 ± 25 beats/min). In conclusion, the cardiac component of the baroreceptor reflex is likely responsible for the chronotropic differences observed between βARK 2 -/- and WT mice.

Duke Scholars

Published In

FASEB Journal

ISSN

0892-6638

Publication Date

1998

Volume

12

Issue

4

Start / End Page

A396

Related Subject Headings

  • Biochemistry & Molecular Biology
  • 3208 Medical physiology
  • 3101 Biochemistry and cell biology
  • 1116 Medical Physiology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology
 

Citation

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Walker, J. K. L., Peppel, K., Lefkowitz, R. J., Caron, M. G., & Fisher, J. T. (1998). Altered cardiac chronotropic responses in βARK 2 knockout mice. FASEB Journal, 12(4), A396.
Walker, J. K. L., K. Peppel, R. J. Lefkowitz, M. G. Caron, and J. T. Fisher. “Altered cardiac chronotropic responses in βARK 2 knockout mice.” FASEB Journal 12, no. 4 (1998): A396.
Walker JKL, Peppel K, Lefkowitz RJ, Caron MG, Fisher JT. Altered cardiac chronotropic responses in βARK 2 knockout mice. FASEB Journal. 1998;12(4):A396.
Walker, J. K. L., et al. “Altered cardiac chronotropic responses in βARK 2 knockout mice.” FASEB Journal, vol. 12, no. 4, 1998, p. A396.
Walker JKL, Peppel K, Lefkowitz RJ, Caron MG, Fisher JT. Altered cardiac chronotropic responses in βARK 2 knockout mice. FASEB Journal. 1998;12(4):A396.

Published In

FASEB Journal

ISSN

0892-6638

Publication Date

1998

Volume

12

Issue

4

Start / End Page

A396

Related Subject Headings

  • Biochemistry & Molecular Biology
  • 3208 Medical physiology
  • 3101 Biochemistry and cell biology
  • 1116 Medical Physiology
  • 0606 Physiology
  • 0601 Biochemistry and Cell Biology