K IR channels mediate parenchymal arteriole dilation to extracellular potassium

Abstract

Astrocytes, in response to increases in neuron activity, release vasoactive substance(s) from perivascular endfeet to dilate cortical parenchymal arterioles (PAs) and drive local changes in cerebral blood flow. Recent evidence indicates astrocytic endfeet exhibit preferential expression of Ca2+-sensitive K+ (BKCa) channels, and we have measured significant BKCa currents from endfeet. However, potential PA smooth muscle targets for localized release of K+ from endfeet BKCa channels remain unclear. Elevation of [K+]o could dilate PAs by activating Na+/K+ATPases and/or inward rectifier K+ (KIR) channels to cause membrane hyperpolarization and a reduction in cytosolic Ca2+ concentration ([Ca2+]c). To investigate this, PAs were dissected from rat cerebral cortex and vascular smooth muscle cells were isolated for patch clamp studies. KIR currents were observed, as well as BKCa and KV currents. Ba2+–sensitive (100 μM) KIR current density at −100 mV was more pronounced for PA versus pial arteries (> 5 pA/pF difference at 60 mM [K+]o), with some PA cells exhibiting large KIR currents. Furthermore, we investigated the effects of [K+]o on pressurized (40 mm Hg) PA diameter, Em and [Ca2+]c. Increasing [K+]o from 3 to 8 mM hyperpolarized the smooth muscle, reduced [Ca2+]c and elicited a 38% dilation that could be blocked by exposure to 30 μM Ba2+, but not by the selective Na+/K+ATPase inhibitor dihydro-ouabain (30 μM). These data indicate KIR are responsible for [K+]o–induced dilations in PAs and suggest a key role for smooth muscle KIR channels in neurovascular coupling by mediating arteriolar dilations in response to neuron activation. Supported by NIH HL44455.