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 (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-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). BKCa 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 BKCa 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 BKCa-dependent STOCs in Old may represent an adaptation of resistance arteries to maintain functional integrity.

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

“…Similar results have been reported in a large number of different preparations studied by pressure myography including rat tail arteries (1270), rat saphenous arteries (116), rabbit renal arcuate arteries (1176), canine subepicardial arteries (191), canine coronary arterioles (1210), first-order hamster (1596) or rat cremaster arterioles (629, 785), rat small mesenteric arteries (677, 911), hamster (1528), or murine (1527) cremaster muscle feed arteries and second-order arterioles, and murine superior epigastric arteries (573). Charybdotoxin contracts rings of porcine coronary arteries (467) and strips of rat femoral and mesenteric arteries (65) and enhances stretch-induced myogenic tone of dog basilar (66), middle cerebral (65), posterior cerebral (65), and coronary (65) artery strips.…”

“…However, they did not establish a physiological function for these events. Subsequently, STOCs were identified in many vascular SMC preparations including, but not limited to: rabbit portal vein (104), hog carotid artery (329), guinea pig coronary artery (458), porcine coronary arteries (1333), rat basilar arteries (1338), human mesenteric arteries (1311), bovine coronary arteries (1334), rat cerebral arteries (1071), rat aorta (888), human coronary arteries (484), guinea pig mesenteric and submucosal arterioles (598), rat hepatic arteries (1660), canine renal arteries (663), rat renal arteries (131), mouse cerebral arteries (1168), rat mesenteric arteries (850), rat tail artery (243), porcine coronary arterioles (1020), guinea pig mesenteric arteries (1178), rat coronary arteries (264), rabbit basilar artery (1132), rat saphenous arteries (428), rat cremaster first-order arterioles (1589), and mouse superior epigastric arteries (573). …”

Caloric restriction confers persistent anti-oxidative, pro-angiogenic, and anti-inflammatory effects and promotes anti-aging miRNA expression profile in cerebromicrovascular endothelial cells of aged rats

“…Despite recent advances in redox biology and aging research (9,21,27,33,37,49,51,52,55,59,65,72,97), the role of ROS in the cerebromicrovascular effects of CR remains elusive. To assess cellular peroxide production, we used the cell-permeant oxidative fluorescent indicator dye CM-H 2DCFDA [5 (and 6)-chloromethyl-2=,7=-dichlorodihydrofluorescein diacetateacetyl ester; Invitrogen, Carlsbad, CA] as we previously reported (16,86).…”

Calcium and electrical signaling in arterial endothelial tubes: New insights into cellular physiology and cardiovascular function

“…These vasodilatory processes are additionally modulated by endothelial mitochondria and reactive oxygen species production (140, 141). Indeed, BK Ca channel function has been demonstrated to increase in smooth muscle cells of mouse superior epigastric arteries of old mice (24 to 26 months) (15). Finally, conclusions between studies can differ based on a lack of awareness for structural changes of the vasculature (e.g., arterial stiffening, smooth muscle hypertrophy) that occur alongside ion channel activity during aging (15-17, 131).…”