Modulation of voltage-dependent K+ channel current in vascular smooth muscle cells from rat mesenteric arteries

J Membr Biol. 2001 Mar 15;180(2):163-75. doi: 10.1007/s002320010067.


Voltage-dependent K+ (Kv) channels were studied in smooth muscle cells (SMCs) freshly isolated from rat mesenteric arteries. A delayed outward rectifier Kv current (IK) with a weak voltage dependence was identified. The amplitude of IK, but not its inactivation kinetics, was inhibited by 4-aminopyridine (4-AP) (IC50, 5.1 +/- 0.9 mM). The inhibitory effect of 4-AP was not use-dependent, and the unbinding of 4-AP from IK channels was complete in the absence of depolarization stimuli, suggesting the binding of 4-AP to the closed state of Kv channels. There was no change in the steady-state inactivation, but the steady-state activation curve of IK was shifted in the presence of 4-AP by +6 mV. Including 4-AP in pipette solution instantly inhibited IK upon the rupture of cell membrane, indicating that 4-AP bound to the inner mouth of Kv channel pores. Several Kv channel proteins encoding the native IK-type Kv channels, but not the transient outward A-type Kv channels, were identified. Among the identified IK-encoding gene transcripts, the expression of Kv1.5 was the most abundant. Our results elucidate the modulating mechanisms for the 4-AP-induced IK inhibition in rat mesenteric artery SMCs and suggest that the unique properties of Kv channels in these cells might be related to the heteromeric expression of the IK-encoding genes with Kv1.5 subunit playing an important role.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / pharmacology*
  • Animals
  • Brain / physiology
  • Cells, Cultured
  • Charybdotoxin / pharmacology
  • Immunoblotting
  • Kinetics
  • Male
  • Mesenteric Arteries / cytology*
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / metabolism*
  • Patch-Clamp Techniques
  • Peptides / pharmacology
  • Potassium Channels / drug effects
  • Potassium Channels / genetics
  • Potassium Channels / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Tetraethylammonium / pharmacology


  • Peptides
  • Potassium Channels
  • Charybdotoxin
  • Tetraethylammonium
  • iberiotoxin
  • 4-Aminopyridine