Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure

Simon Bulley, Carlos Fernández-Peña, Raquibul Hasan, Marie Dennis Leo, Padmapriya Muralidharan, Charles E. Mackay, Kirk W. Evanson, Luiz Moreira-Junior, Alejandro Mata Daboin, Sarah K. Burris, Qian Wang, Korah P. Kuruvilla, Jonathan Jaggar

Research output: Contribution to journalArticle

Abstract

Systemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension in vivo. We generated the first inducible, smooth muscle-specific knockout mice for a TRP channel, namely for PKD2 (TRPP1), to investigate arterial myocyte and blood pressure regulation by this protein. Using this model, we show that intravascular pressure and a 1 -adrenoceptors activate PKD2 channels in arterial myocytes of different systemic organs. PKD2 channel activation in arterial myocytes leads to an inward Na + current, membrane depolarization and vasoconstriction. Inducible, smooth muscle cell-specific PKD2 knockout lowers both physiological blood pressure and hypertension and prevents pathological arterial remodeling during hypertension. Thus, arterial myocyte PKD2 controls systemic blood pressure and targeting this TRP channel reduces high blood pressure.

Original languageEnglish (US)
Article numbere42628
JournaleLife
Volume7
DOIs
StatePublished - Dec 1 2018

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Blood pressure
Muscle Cells
Smooth Muscle Myocytes
Muscle
Transient Receptor Potential Channels
Cells
Blood Pressure
Hypertension
Pressure regulation
Vasoconstriction
Knockout Mice
Adrenergic Receptors
Depolarization
Smooth Muscle
Arterial Pressure
Proteins
Pressure
Chemical activation
Membranes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Bulley, S., Fernández-Peña, C., Hasan, R., Leo, M. D., Muralidharan, P., Mackay, C. E., ... Jaggar, J. (2018). Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure. eLife, 7, [e42628]. https://doi.org/10.7554/eLife.42628

Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure. / Bulley, Simon; Fernández-Peña, Carlos; Hasan, Raquibul; Leo, Marie Dennis; Muralidharan, Padmapriya; Mackay, Charles E.; Evanson, Kirk W.; Moreira-Junior, Luiz; Mata Daboin, Alejandro; Burris, Sarah K.; Wang, Qian; Kuruvilla, Korah P.; Jaggar, Jonathan.

In: eLife, Vol. 7, e42628, 01.12.2018.

Research output: Contribution to journalArticle

Bulley, S, Fernández-Peña, C, Hasan, R, Leo, MD, Muralidharan, P, Mackay, CE, Evanson, KW, Moreira-Junior, L, Mata Daboin, A, Burris, SK, Wang, Q, Kuruvilla, KP & Jaggar, J 2018, 'Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure', eLife, vol. 7, e42628. https://doi.org/10.7554/eLife.42628
Bulley S, Fernández-Peña C, Hasan R, Leo MD, Muralidharan P, Mackay CE et al. Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure. eLife. 2018 Dec 1;7. e42628. https://doi.org/10.7554/eLife.42628
Bulley, Simon ; Fernández-Peña, Carlos ; Hasan, Raquibul ; Leo, Marie Dennis ; Muralidharan, Padmapriya ; Mackay, Charles E. ; Evanson, Kirk W. ; Moreira-Junior, Luiz ; Mata Daboin, Alejandro ; Burris, Sarah K. ; Wang, Qian ; Kuruvilla, Korah P. ; Jaggar, Jonathan. / Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure. In: eLife. 2018 ; Vol. 7.
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