Molecular determinants of beta‐adrenergic signaling to voltage‐gated K⁺ channels in the cerebral circulation

Abstract

Voltage-gated K + (K v ) channels are major determinants of membrane potential in vascular smooth muscle cells (VSMCs) and regulate the diameter of small cerebral arteries and arterioles. However, the intracellular structures that govern the expression and function of vascular K v channels are poorly understood. Scaffolding proteins including postsynaptic density 95 (PSD95) recently were identified in rat cerebral VSMCs.Primarily characterized in neurons, the PSD95 scaffold has more than 50 known binding partners, and it can mediate macromolecular signaling between cell-surface receptors and ion channels. In cerebral arteries, Shaker-type K v 1 channels appear to associate with the PSD95 molecular scaffold, and PSD95 is required for the normal expression and vasodilator influence of members of this K + channel gene family. Future investigations into these macromolecular complexes that modulate the expression and function of K v channels may reveal unknown signaling cascades that regulate VSMC excitability and provide novel targets for ion channel-based medications to optimize vascular tone. K E Y W O R D Sbeta adrenergic receptors, potassium channels, scaffolding proteins, smooth muscle

Ion channel molecular complexes in vascular smooth muscle

“…PSD95 was found to colocalize with the β1-adrenergic Frontiers in Physiology frontiersin.org receptor in VSM and to enable phosphorylation of K V 1 channels by PKA in rat cerebral VSM (Joseph et al, 2011;Moore et al, 2014). Thus, in cerebral VSM, PSD95 facilitates β-adrenergicmediated vasodilatory regulation via the formation of a macromolecular complex with K V 1 channels (Moore et al, 2015;Rhee and Rusch, 2018) (Figure 3). Whether other scaffolds are involved in K V channel regulation in VSM is an area for further research development in VSM.…”

Hydrogen Sulfide-Induced Vasodilation: The Involvement of Vascular Potassium Channels

“…α-subunits form the ion conducting pore and β-subunits modulate the activity of α-subunits. K V channels are major determinants of membrane potential and play a key role in regulating vascular dilation ( Rhee and Rusch, 2018 ). And the distribution of K V1 , K V7 , and K V9.3 are reported in vascular smooth muscle cells of different vessel beds ( Nieves-Cintrón et al, 2018 ).…”