Tuning electrical conduction along endothelial cell tubes via Ca2+‐activated K+ channels

Abstract

Electrical conduction along coupled cells reflects low axial resistance (ra) of gap junction channels (GJCs) and high plasma membrane resistance (rm) to current flow. Manipulating GJCs alters conducted vasomotor responses but little is known of how conduction may be governed by membrane ion channel activation. We hypothesized that Ca2+‐activated K+ channels (SKCa/IKCa) can tune rm to regulate electrical conduction along endothelial cell (EC) tubes (width, 60 μm; length, ≥ 2 mm) isolated from feed arteries of C57BL/6 mouse skeletal muscle (n = 6–10 males). Using dual simultaneous intracellular microelectrodes, membrane potential (Vm) was uniform along EC tubes (−25 ± 2 mV) and propidium iodide dye injected into one EC spread throughout neighbouring ECs. Conduction amplitude (CA = ΔVm at Site 2/nA current injected at Site 1) decreased with electrode separation distance (CA = 11, 8, 6, 4, 3 ± 1 mV/nA at 50, 500, 1000, 1500, 2000 μm). The SKCa/IKCa activator NS309 (1μM) reduced length constant [λ = (rm/ra)½] from 1360 ± 80 to 840 ± 60 μm (P<0.05). With electrode separation = 500 μm, NS309 from 0.01 to 10 μM increased Vm from −28 ± 1 to −81 ± 1 mV and abolished CA while dye transfer was maintained; blocking SKCa/IKCa (300 nM apamin + 100 nM charybdotoxin) increased CA by ~30% (P<0.05). We conclude that the effectiveness of electrical conduction can be tuned through SKCa/IKCa activation. (NIH R37HL041026, R01HL086483, F32HL110701)