K+ currents in human coronary artery vascular smooth muscle cells.
K+ channels and their currents are important in vascular tone regulation and are potential therapeutic targets; however, K+ channels in human coronary artery vascular smooth muscle cells (VSMCs) have received little attention. We examined K+ currents in freshly isolated VSMCs from human coronary arteries (n=368 from 32 human hearts) with conventional patch-clamp or perforated-patch techniques with nystatin. We detected four different K+ currents: (1) the delayed rectifier K+ current, IK(dr); (2) the Ca2+-activated K+ current, IK(Ca); (3) the nonrectifying noninactivating outward ATP-dependent K+ current, IK(ATP); and (4) the spontaneous transient outward K+ current, IK(STOC). K+ channels underlying spontaneous transient outward currents probably represent a single clustered population of Ca2+-activated K+ channels functionally associated with Ca2+ release channels in the sarcoplasmic reticulum. Inwardly rectifying K+ currents were not observed. K+ currents were unevenly distributed in that they were not uniformly exhibited by all cells. The most prominent K+ currents were IK(Ca) (100%) and IK(dr) (46%). IK(STOC)s, which have not been previously described in humans, were present in 67% of VSMCs. IK(ATP) was small under physiological conditions; however, IK(ATP) increased markedly after cell stimulation with exogenous or endogenous coronary vasodilators. Thus, IK(ATP) may be particularly relevant in ischemia and could be of special importance as a therapeutic target. We conclude that human coronary VSMCs have unique K+ currents that differ sufficiently from those of other species, thus making the investigation of human material clinically relevant. The findings suggest potential avenues for further therapeutic research.
Gollasch
M
M
Franz Volhard Clinic, Virchow Klinikum at the Max Delbrück Center for Molecular Medicine, Humboldt University of Berlin, Germany.
Ried
C
C
Bychkov
R
R
Luft
F C
FC
Haller
H
H
D000255:Adenosine Triphosphate / Q000502:physiology; D001158:Arteries / Q000166:cytology / Q000502:physiology; D002118:Calcium / Q000502:physiology; D002469:Cell Separation; D003331:Coronary Vessels / Q000166:cytology / Q000502:physiology*; D004553:Electric Conductivity; D005260:Female; D006801:Humans; D008297:Male; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D011188:Potassium / Q000502:physiology*; D015221:Potassium Channels / Q000502:physiology*; D011930:Reaction Time
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D011188:Potassium; D002118:Calcium