Aging Impairs Electric Conduction Along Endothelium of Resistance Arteries Through Enhanced Calcium-Activated K+ Channel Activation
Objective—Intercellular conduction of electric signals underlies spreading vasodilation of resistance arteries. Small- and intermediate-conductance Ca2+-activated K+ channels of endothelial cells serve a dual function by initiating hyperpolarization and modulating electric conduction. We tested the hypothesis that regulation of electric signaling by small- and intermediate-conductance Ca2+-activated K+ channels is altered with advancing age.
Approach and Results—Intact endothelial tubes (60 µm wide; 1–3 mm long) were freshly isolated from male C57BL/6 mouse (young: 4–6 months; intermediate: 12–14 months; old: 24–26 months) superior epigastric arteries. Using dual intracellular microelectrodes, current was injected (±0.1–3 nA) at site 1 while recording membrane potential (Vm) at site 2 (separation distance: 50–2000 µm). Across age groups, greatest differences were observed between young and old. Resting Vm in old (−38±1 mV) was more negative (P<0.05) than young (−30±1 mV). Maximal hyperpolarization to both direct (NS309) and indirect (acetylcholine) activation of small- and intermediate-conductance Ca2+-activated K+ channels was sustained (ΔVm ≈−40 mV) with age. The length constant (λ) for electric conduction was reduced (P<0.05) from 1630±80 µm (young) to 1320±80 µm (old). Inhibiting small- and intermediate-conductance Ca2+-activated K+ channels with apamin+charybdotoxin or scavenging hydrogen peroxide (H2O2) with catalase improved electric conduction (P<0.05) in old. Exogenous H2O2 (200 µmol/L) in young evoked hyperpolarization and impaired electric conduction; these effects were blocked by apamin+charybdotoxin.
Conclusions—Enhanced current loss through KCa activation impairs electric conduction along the endothelium of resistance arteries with aging. Attenuating the spatial domain of electric signaling will restrict the spread of vasodilation and thereby contribute to blood flow limitations associated with advanced age.
- Received March 11, 2013.
- Accepted May 14, 2013.
- © 2013 American Heart Association, Inc.