Blocking of cloned and native delayed rectifier K channels from visceral smooth muscles by phencyclidine.
We investigated the effect of phencyclidine (PCP) on three native delayed rectifier K+ currents and three channels cloned from canine and human circular colonic myocytes using voltage-clamp techniques. Native delayed rectifier K+ current in canine circular colon is composed of at least three components: (i) a rapidly activating, 4-aminopyridine-sensitive component (termed IdK(f)); (ii) a slowly activating, tetraethylammonium (TEA)-sensitive component (IdK(s)); and (iii) a rapidly activating, TEA-sensitive component, which has a steady-state inactivation curve shifted towards more negative potentials (IdK(n)). PCP blocked all three components with EC50 values of 45, 27 and 59 micromol L-1, respectively. Blocking was neither use-dependent nor voltage-dependent. Delayed rectifier K+ channels cloned from canine (Kv1.2, Kv1.5) and from human (Kv2.2) colon were expressed in Xenopus oocytes. PCP blocked all three currents with similar potency. In contrast, PCP (up to 10-4 mol L-1) did not reduce the magnitude of Ca2+-dependent outward current of large conductance Ca2+-activated K+ channels (BK channels).
Frey
B W
BW
Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, USA.
Lynch
F T
FT
Kinsella
J M
JM
Horowitz
B
B
Sanders
K M
KM
Carl
A
A
D000818:Animals; D002118:Calcium / Q000378:metabolism; D003001:Cloning, Molecular; D003106:Colon / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D051668:Delayed Rectifier Potassium Channels; D004285:Dogs; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology; D009130:Muscle, Smooth / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010622:Phencyclidine / Q000494:pharmacology*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D051669:Shab Potassium Channels; D014982:Xenopus laevis
D051668:Delayed Rectifier Potassium Channels; D018691:Excitatory Amino Acid Antagonists; C496992:KCNB2 protein, human; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D051669:Shab Potassium Channels; D000242:Cyclic AMP; D010622:Phencyclidine; D002118:Calcium