Aging increases the amplitude of spontaneous transient outward currents in murine resistance artery smooth muscle cells

Abstract

Large conductance Ca2+‐activated K+ channels (BKCa) contribute to negative feedback regulation of microvascular tone. However, the effects of aging on BKCa function are unclear. The purpose of this study was to determine: 1) if enzymatically‐isolated smooth muscle cells (SMCs) from skeletal muscle resistance arteries display BKCa‐ and ryanodine receptor (RyR)‐dependent spontaneous transient outward currents (STOCs); and 2) whether aging affects STOC properties. Using perforated patch clamp recording, individual SMCs from Young (≥ 3 months) and Old (≥ 24 months) male C57BL/6 mice displayed STOCs at membrane potentials ≥ −30 mV, with the amplitude and frequency of STOCs increasing with membrane depolarization (n = 19–24; p < 0.05). STOCs were inhibited by BKCa channel blockers (1 μM paxilline, 100 nM iberiotoxin) and by a RyR antagonist (100 μM tetracaine) (n ≥ 5; p < 0.05 each). At +30 mV holding potential, STOC amplitude = 3.2 ± 0.32 pA/pF and frequency = 3.88 ± 0.41 Hz (n = 67) in SMCs from Young. STOC amplitude increased to 4.97 ± 0.5 pA/pF (n = 61; p < 0.05) in SMCs from Old, with no significant difference in frequency (3.15 ± 0.31 Hz; p >; 0.05). SMCs from murine resistance arteries display BKCa‐ and RyR‐dependent STOCs and aging increases STOC amplitude. Age‐related change in BKCa activity may impact the regulation of SMC function and contribute to age‐induced alterations in muscle blood flow regulation. (NIH R01HL086483).