Journal
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
Volume 306, Issue 11, Pages H1512-H1524Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00492.2013
Keywords
aging; resistance arteries; potassium channels; vascular smooth muscle; myogenic tone
Funding
- National Heart, Lung, and Blood Institute (NHLBI) [RO1-HL-086483]
- NHLBI Research Education [R25-HL-103156]
- Michigan State University College of Veterinary Medicine Summer Research Program
- Michael A. Hill
- NHLBI [R01 HL-092241]
- [5F32 HL-118836]
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Large conductance Ca2+-activated K+ channels (BKCa) contribute to negative feedback regulation of smooth muscle cell (SMC) tone. However, the effects of aging on BKCa function are unclear. We tested the hypothesis that aging alters SMC BKCa 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-moold 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). BKCa blockers (1 mu M paxilline, 100 nM iberiotoxin, 1 mM tetraethylammonium) or a ryanodine receptor antagonist (100 mu M tetracaine) inhibited STOCs (n >= 6; P < 0.05 each). Western blots revealed increased expression of BKCa alpha-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 BKCa-dependent STOCs in Old may represent an adaptation of resistance arteries to maintain functional integrity.
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