Traumatic Brain Injury Alters BK Channel Subunit Expression, Localization, and Function in Cerebral Arterial Myocytes

Abstract

Traumatic brain injury (TBI) induces acute changes in cerebrovascular function, which include alterations to cerebral artery myogenic tone and autoregulation. In arterial smooth muscle cells (myocytes), large‐conductance calcium‐activated potassium (BK) channels play a vital role in modulating plasma membrane potential and myogenic tone. Here, we examined BK channel expression and function in cerebral resistance size arteries one week following moderately‐severe TBI induced by controlled cortical impact with craniotomy. Total BKα (pore‐forming) and β1 (regulatory) subunit expression were reduced one week post‐TBI. Biotinylation of plasma membrane‐bound proteins revealed a compensatory increase of β1 subunits to the plasma membrane following TBI, which normalized single BK channel activation as assessed using patch‐clamp electrophysiology. However, the loss of total BKα subunits resulted in diminished whole cell, transient BK currents. Pressurized cerebral arteries from TBI rats exhibited greater myogenic tone at 60 mmHg and a diminished response to iberiotoxin, a BK channel pore blocker. In conclusion, moderately‐severe TBI enhances cerebral artery contractility, in part, through reductions in arterial myocyte BK channel subunit expression and function. Moreover, these TBI‐induced alterations in cerebral artery function can persist well beyond the initial 24–48 hour period post‐injury.Support or Funding InformationFlorida State UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.