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

Tytuł:: Arterial smooth muscle cell PKD2 (TRPP1) channels regulate systemic blood pressure.
Autorzy:: Bulley S; Department of Physiology, University of Tennessee Health Science Center, Memphis, United States.
Fernández-Peña C; Department of Physiology, University of Tennessee Health Science Center, Memphis, United States.
Hasan R; Department of Physiology, University of Tennessee Health Science Center, Memphis, United States.
Leo MD; Department of Physiology, University of Tennessee Health Science Center, Memphis, United States.
Muralidharan P; Department of Physiology, University of Tennessee Health Science Center, Memphis, United States.
Mackay CE; Department of Physiology, University of Tennessee Health Science Center, Memphis, United States.
Evanson KW; Department of Physiology, University of Tennessee Health Science Center, Memphis, United States.
Moreira-Junior L; Department of Physiology, University of Tennessee Health Science Center, Memphis, United States.
Mata-Daboin A; Department of Physiology, University of Tennessee Health Science Center, Memphis, United States.
Burris SK; Department of Physiology, University of Tennessee Health Science Center, Memphis, United States.
Wang Q; Department of Physiology, University of Tennessee Health Science Center, Memphis, United States.
Kuruvilla KP; Department of Physiology, University of Tennessee Health Science Center, Memphis, United States.
Jaggar JH; Department of Physiology, University of Tennessee Health Science Center, Memphis, United States.
Źródło:: ELife [Elife] 2018 Dec 04; Vol. 7. Date of Electronic Publication: 2018 Dec 04.
Typ publikacji:: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
MeSH Terms:: Arteries/*metabolism
Hypertension/*genetics
Myocytes, Smooth Muscle/*metabolism
Receptors, Adrenergic, alpha-1/*genetics
Sodium/*metabolism
TRPP Cation Channels/*genetics
Animals ; Arteries/physiopathology ; Blood Pressure/physiology ; Cations, Monovalent ; Gene Expression Regulation ; Hindlimb/blood supply ; Hindlimb/cytology ; Hypertension/metabolism ; Hypertension/physiopathology ; Ion Transport ; Membrane Potentials/physiology ; Mice ; Mice, Knockout ; Myocytes, Smooth Muscle/pathology ; Receptors, Adrenergic, alpha-1/metabolism ; Signal Transduction ; TRPP Cation Channels/deficiency ; Vasoconstriction/physiology
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Grant Information:: R01 HL137745 United States HL NHLBI NIH HHS; P30 DK090868 United States DK NIDDK NIH HHS; R01 HL067061 United States HL NHLBI NIH HHS; HL137745 United States HL NHLBI NIH HHS; R01 HL133256 United States HL NHLBI NIH HHS; HL133256 United States HL NHLBI NIH HHS; HL67061 United States HL NHLBI NIH HHS
Contributed Indexing:: Keywords: PKD2; blood pressure; hypertension; mouse; neuroscience; physics of living systems; smooth muscle
Substance Nomenclature:: 0 (Cations, Monovalent)
0 (Receptors, Adrenergic, alpha-1)
0 (TRPP Cation Channels)
0 (polycystic kidney disease 2 protein)
9NEZ333N27 (Sodium)
Entry Date(s):: Date Created: 20181205 Date Completed: 20190314 Latest Revision: 20200702
Update Code:: 20240105
PubMed Central ID:: PMC6281320
DOI:: 10.7554/eLife.42628
PMID:: 30511640
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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 α 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.
Competing Interests: SB, CF, RH, ML, PM, CM, KE, LM, AM, SB, QW, KK, JJ No competing interests declared
(© 2018, Bulley et al.)

Erratum in: Elife. 2020 Jun 30;9:. (PMID: 32602835)

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