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Aging impairs electrical conduction along resistance artery endothelium via enhanced signal dissipation through K Ca channels
Author(s) -
Behringer Erik,
Segal Steven
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.861.2
Subject(s) - charybdotoxin , chemistry , apamin , depolarization , membrane potential , medicine , endocrinology , nuclear magnetic resonance , biophysics , calcium , biochemistry , biology , physics , organic chemistry
Aging results in endothelial cell (EC) dysfunction yet little is known of how intercellular transmission of electrical signals is affected. We hypothesized that aging impairs electrical conduction via current dissipation through Ca 2+ ‐activated K + channels (SK Ca /IK Ca ). EC tubes (width: 60 μm; length: ≥ 2 mm) isolated from Young (3–6 mo, n ≥ 10) and Old (24–26 mo, n ≥ 8) superior epigastric arteries of male C57BL/6 mice were studied using dual simultaneous intracellular microelectrodes placed at separation distances of 50–2000 μm. Membrane potential (V m ) was greater in Old (−35 ± 2) vs. Young (−26 ± 1 mV; P < 0.05). Conduction amplitude (CA; ΔV m at Site 2/nA current injected at Site 1) was less in Old vs. Young (at 500 μm: 6 ± 1 vs. 10 ± 1 mV/nA; P < 0.05). SK Ca /IK Ca activation (1 μM NS309) increased V m similarly for Old (Δ = −32 ± 2) and Young (Δ = −35 ± 2 mV) and the reduction in CA was greater in Young vs. Old (−6 ± 1 vs. −4 ± 1 mV/nA; P < 0.05). SK Ca /IK Ca inhibition (300 nM apamin + 100 nM charybdotoxin) evoked greater depolarization in Old (Δ = 14 ± 2) vs. Young (Δ = 7 ± 1 mV; P < 0.05) and the resulting increase in CA was greater in Old (45 ± 7%) vs. Young (22 ± 6%; P < 0.05) which restored conduction in Old to that of Young (both = 10 ± 1 mV/nA). We conclude that aging impairs electrical conduction along the endothelium by increasing signal dissipation through enhanced SK Ca /IK Ca activation. (NIH R01HL086483, R37HL041026, F32HL110701)