Copyright © 2006, European Society of Cardiology
Membrane potassium currents in human radial artery and their regulation by nitric oxide donor
aDepartment of Medicine, McMaster University, 50 Charlton Avenue East, Hamilton, Ontario, Canada L8N 4A6
bDepartment of Surgery, McMaster University, Hamilton, Ontario, Canada L8N 4A6
* Corresponding author. Tel.: +1 905 522 1155x5912; fax: +1 905 540 6510. Email address: janssenl{at}mcmaster.ca
Objective The human radial artery has demonstrated superior long-term results as a graft in coronary bypass surgery, but undesirable post-surgical spasm limits its clinical application. Few have examined its excitatory properties, especially the underlying ion channel mechanisms. In this study, we investigated the kinetic and pharmacological properties of the smooth muscle membrane potassium currents of this important artery.
Methods and results Using whole cell patch-clamp techniques, we found the K+ current to be voltage-dependent and outwardly rectifying. Voltage-dependent inactivation was observed, being half-maximal at +28.0 mV but incomplete even at +40 mV. The K+ currents were predominantly sensitive to the KCa blocker tetraethylammonium (TEA; 63.9±12.1% inhibition, p<0.05), less sensitive to the Kv blocker 4-aminopyridine (4-AP; 32.8±4.4% inhibition, p<0.05), and the KATP blocker glibenclamide (28.7±8.5% inhibition), at – 20 mV testing potential. Resting membrane potential was – 52.0±6.8 mV (n=5), and suppression of K+ currents by TEA and iberiotoxin (IbTx) caused membrane depolarization. Western blot analysis with channel-specific antibodies confirmed the presence of KCa and Kv channel proteins. TEA evoked 20.7±9.9% of the contractile response to 60 mM KCl, whereas IbTx caused about 10% of the above response at 10– 7 M. The nitric oxide donor SNAP augmented membrane K+ currents in a concentration-dependent fashion; the augmentation was completely suppressed by TEA, but was relatively insensitive to the guanylate cyclase inhibitor ODQ.
Conclusions The radial artery manifests mainly Ca2+-dependent K+ currents at rest; this current is augmented by nitric oxide through a cGMP- and protein kinase G-independent action. The relatively depolarized membrane potential, as well as its muscular structure, predisposes the radial artery to spasm. Agents that activate the Ca2+-dependent K+ current could be of therapeutic value in preventing post-surgical vasospasm.
KEYWORDS K+ current; Voltage-dependent; Ca2+-activated; ATP-sensitive; Nitric oxide
Time for primary review 19 days
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