Aging increases capacitance and spontaneous transient outward current amplitude of smooth muscle cells from murine superior epigastric arteries

Abstract

Large conductance Ca 2+ -activated K + channels (BK Ca ) contribute to negative feedback regulation of smooth muscle cell (SMC) tone. However, the effects of aging on BK Ca function are unclear. We tested the hypothesis that aging alters SMC BK Ca function in superior epigastric arteries (SEAs) by using perforated patch recording of enzymatically isolated SMCs from 3- to 4-mo-old male C57BL/6 mice (Young) and 24- to 26-mo-old male C57BL/6 mice (Old). SMC capacitance from Young (15.7 ± 0.4 pF; n = 110) was less than Old (17.9 ± 0.5 pF; n = 104) ( P < 0.05). SMCs displayed spontaneous transient outward currents (STOCs) at membrane potentials more positive than −30 mV; depolarization increased STOC amplitude and frequency ( P < 0.05; n = 19–24). STOC frequency in Young (2.2 ± 0.6 Hz) was less than Old (4.2 ± 0.7 Hz) at −10 mV ( P < 0.05, n = 27–30), with no difference in amplitude (1.0 ± 0.1 vs. 0.9 ± 0.1 pA/pF, respectively). At +30 mV, STOC amplitude in Young (3.2 ± 0.3 pA/pF) was less than Old (5.0 ± 0.5 pA/pF; P < 0.05, n = 61–67) with no difference in frequency (3.9 ± 0.4 vs. 3.2 ± 0.3 Hz, respectively). BK Ca blockers (1 μM paxilline, 100 nM iberiotoxin, 1 mM tetraethylammonium) or a ryanodine receptor antagonist (100 μM tetracaine) inhibited STOCs (n ≥ 6; P < 0.05 each). Western blots revealed increased expression of BK Ca α-subunit protein in Old. Pressure myography revealed no effect of age on SEA maximal diameter, myogenic tone, or paxilline-induced constriction ( n = 10–12; P > 0.05). Enhanced functional expression of SMC BK Ca -dependent STOCs in Old may represent an adaptation of resistance arteries to maintain functional integrity.