Advanced Age Increases the Amplitude of ATP‐sensitive K + Channel Currents in Murine Resistance Artery Smooth Muscle Cells

Abstract

Advanced age impairs skeletal muscle blood flow regulation. We tested the hypothesis that advanced age decreases ATP-sensitive K+ channel (KATP) function of smooth muscle cells (SMCs) in skeletal muscle resistance arteries. Superior epigastric arteries (SEAs) were dissected from Young (Y; 蠅3 mo) or Old (O; 蠅24 mo) male C57BL/6 mice and either dissociated to yield individual SMCs for perforated patch clamp recording (holding potential, -30 mV) or cannulated and pressurized to 80 cm H20 for pressure myography. The KATP antagonist, glibenclamide (Glib, 10 µM) blocked small outward currents that were similar in Y and O (0.25±0.08 vs. 0.12±0.09 pA/pF, n = 6, p > 0.05). The KATP agonist levcromakalim (Lev, 10 µM) activated Glib-sensitive outward currents that were smaller in Y than O (0.14±0.05 vs. 1.11±0.37 pA/pF, n = 6, p < 0.05). However, Glib (10 µM) had no effect on resting diameter of SEAs from Y (control: 161±5; Glib: 166±5 μm, n=11, p>0.05) or O (control: 155±12; Glib: 155±11 μm, n=4, p>0.05). Lev induced similar maximal dilation in SEAs from Y (80±4%, n = 11) and O (74±12%, n = 7) with no difference in sensitivity (LogEC50: -6.98±0.12 vs. -6.83±0.23, p > 0.05). Thus, advanced age increases the functional expression of KATP in SEA SMCs. We suggest that this effect may not translate into a change in vasomotor function if it compensates for other age-related alterations in the regulation of SEA myogenic tone. (NIH R01-HL086483).