PIP2‐Regulation of Endothelial KIR2.1 Channels in Cerebral Arteries

Abstract

In the cerebral circulation, inwardly rectifying potassium (KIR) channels are robustly expressed in both endothelial and smooth muscle cells. This pattern of expression is unusual for vascular cells that are electrically coupled and it suggests that each pool is differentially regulated driving a distinct subset of physiological responses. In this context, this study characterized the electrical/molecular properties of KIR2.x channels in cerebral arteries and ascertained the importance of phosphatidylinositol‐bis‐phosphate (PIP2), a regulatory phospholipid, in modulating each channel pool. Endothelial and smooth muscle cells were freshly isolated from rat cerebral arteries; patch clamp electrophysiology and Q‐PCR were used to ascertain KIR activity and expression, respectively. Our electrophysiological results highlight that a Ba2+‐sensitive KIR current is present and stable in both cell types. Endothelial current density was ~8 fold greater than smooth muscle (−20 vs −2.5 pA/pF at −100mV) and Q‐PCR revealed that KIR2.x mRNA subunits were present in both cell types, albeit it at variable levels. Intriguingly, KIR channels in endothelial but not smooth muscle cells were PIP2 sensitive; neomycin impaired, and exogenous PIP2 elevated channel activity. In summary, our observations indicate that while endothelial and smooth muscle both expressed KIR channels, they are uniquely regulated by PIP2. A complete picture of the expression/regulation of KIR channels within the vascular wall will provide further advances in our understanding of their role in cerebral blood flow control in health and disease.Support or Funding InformationCanadian Institute of Health Research (CIHR)