title: Membrane potassium currents in human radial artery and their regulation by nitric oxide donor.
abstract: 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.
  
  
  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 K(Ca) 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 K(ATP) 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 K(Ca) 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 Ca(2+)-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 Ca(2+)-dependent K(+) current could be of therapeutic value in preventing post-surgical vasospasm.
authors.affiliation: Department of Medicine, McMaster University, 50 Charlton Avenue East, Hamilton, Ontario, Canada L8N 4A6.
authors.forename: Yongde
authors.initials: Y
authors.lastname: Zhang
authors.forename: Tracy
authors.initials: T
authors.lastname: Tazzeo
authors.forename: Victor
authors.initials: V
authors.lastname: Chu
authors.forename: Luke J
authors.initials: LJ
authors.lastname: Janssen
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western / Q000379:methods; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D010069:Oxadiazoles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D017534:Radial Artery; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D010455:Peptides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D011810:Quinoxalines; C110881:S-nitro-N-acetylpenicillamine; D013757:Tetraethylammonium Compounds; C064719:iberiotoxin; D015761:4-Aminopyridine; D006162:Guanylate Cyclase; D010396:Penicillamine; D005905:Glyburide