PMID: 8938726Jan 1, 1996Paper

Paxilline inhibition of the alpha-subunit of the high-conductance calcium-activated potassium channel

Neuropharmacology
M Sanchez, O B McManus

Abstract

High conductance calcium-activated (maxi-K) channels are potently blocked by a family of indole diterpenes that includes paxilline. Paxilline stimulates binding of charybdotoxin (ChTX) to maxi-K channels in vascular smooth muscle and blocks these channels in electrophysiological experiments (Knaus et al., 1994b). These results suggested that paxilline blocked maxi-K channels at a site distance from the ChTX binding site located near the external entrance to the pore. Here we have examined block of the cloned alpha subunit (slo) of the maxi-K channel in excised membrane patches after internal application of paxilline. Paxilline caused a reversible inhibition of channel currents with slow washout kinetics. In the presence of 10 muM intracellular calcium, paxilline blocked currents elicited by brief voltage pulses with a Ki of 1.9 nM and a Hill coefficient near one. Changing the internal calcium by the fold caused a two to three fold change in the Ki for paxilline block, with less block occurring at high calcium concentrations. Paxilline reduced the maximum of the conductance-voltage relation in a calcium-sensitive manner with less block occurring at high calcium concentrations, and caused a 20 mV depolarizing shift in the midpoin...Continue Reading

References

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Citations

Jul 15, 2011·Pflügers Archiv : European journal of physiology·Ricardo S ScottAntonio R Artalejo
Dec 5, 2012·Pflügers Archiv : European journal of physiology·Petra EhlingThomas Budde
May 13, 2010·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·Jan FrässdorfMarkus W Hollmann
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Apr 5, 2015·Expert Opinion on Therapeutic Targets·Antonio LeoEmilio Russo
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Oct 29, 2014·The Journal of General Physiology·Yu Zhou, Christopher J Lingle

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