Single-channel characterization of the pharmacological properties of the K(Ca2+) channel of intermediate conductance in bovine aortic endothelial cells.
The pharmacological profile of a voltage-independent Ca2+-activated potassium channel of intermediate conductance (IK(Ca2+)) present in bovine aortic endothelial cells (BAEC) was investigated in a series of inside-out and outside-out patch-clamp experiments. Channel inhibition was observed in response to external application of ChTX with a half inhibition concentration of 3.3 +/- 0.3 nm (n = 4). This channel was insensitive to IbTX, but channel block was detected following external application of MgTX and StK leading to the rank order toxin potency ChTX > StK > MgTX >>IbTX. A reduction of the channel unitary current amplitude was also measured in the presence of external TEA, with half reduction occurring at 23 +/- 3 mm TEA (n = 3). The effect of TEA was voltage insensitive, an indication that TEA may bind to a site located on external side of the pore region of this channel. Similarly, the addition of d-TC to the external medium caused a reduction of the channel unitary current amplitude with half reduction at 4.4 +/- 0.3 mm (n = 4). In contrast, application of d-TC to the bathing medium in inside-out experiments led to the appearance of long silent periods, typical of a slow blocking process. Finally, the IK(Ca2+) in BAEC was found to be inhibited by NS1619, an activator of the Ca2+-activated potassium channel of large conductance (Maxi K(Ca2+)), with a half inhibition value of 11 +/- 0.8 micron (n = 4). These results provide evidence for a pharmacological profile distinct from that reported for the Maxi K(Ca2+) channel, with some features attributed to the voltage-gated KV1.2 potassium channel.
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Département de physiologie, Groupe de recherche en transport membranaire, Université de Montréal, C.P. 6128, Succarsale Centre-ville, Montréal, Québec, Canada H3C 3J7.
Garneau
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Sauvé
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D000818:Animals; D001011:Aorta; D001562:Benzimidazoles / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D018999:Charybdotoxin / Q000494:pharmacology; D003064:Cnidarian Venoms; D004553:Electric Conductivity; D004730:Endothelium, Vascular / Q000502:physiology*; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D009498:Neurotoxins / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D024681:Potassium Channels, Calcium-Activated; D012604:Scorpion Venoms; D019789:Tetraethylammonium / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology
D001562:Benzimidazoles; D003064:Cnidarian Venoms; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D009498:Neurotoxins; D010455:Peptides; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D012604:Scorpion Venoms; D018999:Charybdotoxin; C059713:neurotoxin I, Stichodactyla helianthus; C086491:NS 1619; C077910:margatoxin; D019789:Tetraethylammonium; C064719:iberiotoxin; D014403:Tubocurarine