Chemokine (C‐X‐C motif) receptor 4 (CXCR4) activation in rat mesenteric artery myocytes is linked to suppression of Kv7 potassium channel activity

Abstract

Chemokine (C‐X‐C motif) receptor 4 (CXCR4) expressed in arterial smooth muscle cells was recently implicated in the regulation of blood pressure. As a part of a heteromultimeric receptor complex with atypical chemokine receptor 3 and α1‐adrenergic receptors, CXCR4 modulates α1‐adrenergic signaling and function in vascular smooth muscle cells. Furthermore, activation of CXCR4 was found to sensitize rats to α1‐adrenergic receptor‐mediated blood pressure elevation. In neurons, α1‐adrenergic receptor activation has been linked to suppression of M‐currents mediated by Kv7 voltage‐gated potassium channels. Suppression of Kv7 currents has also been implicated as a mechanism of vasoconstrictor signal transduction downstream of Gq/11‐coupled receptor activation in arterial smooth muscle cells. We observed that the CXCR4 agonists CXCL12 (SDF‐1α, 10 nM and 100 nM) and ubiquitin (100 nM and 1 μM) significantly and dose‐dependently inhibit Kv7 potassium currents in freshly isolated mesenteric artery smooth muscle cells (MASMCs) by up to 50%. Pretreatment of MASMCs with the CXCR4 antagonist AMD3100 (1 μM) prevented inhibition of Kv7 current by CXCL12 and ubiquitin. Moreover, proximity ligation assays provided evidence for direct interactions of CXCR4 with Kv7.5 channel α‐subunits in MASMCs. Our findings suggest that Kv7 potassium channels are downstream effectors of CXCR4 receptor activation in arterial smooth muscle cells.Support or Funding InformationThe project described was supported by R01GM107495 (M. Majetschak, PI).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.