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Inhibition of the potassium current IK(SO), in cerebellar granule cells, by the inhibitors of MEK1 activation, PD 98059 and U 0126.

Boyd, David F., Mathie, Alistair (2002) Inhibition of the potassium current IK(SO), in cerebellar granule cells, by the inhibitors of MEK1 activation, PD 98059 and U 0126. Neuropharmacology, 42 (2). pp. 221-228. (doi:10.1016/S0028-3908(01)00168-X) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:5691)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
Official URL:
http://dx.doi.org/10.1016/S0028-3908(01)00168-X

Abstract

IK(SO) is a standing-outward potassium current found in cerebellar granule neurons which is inhibited by the activation of muscarinic M(3) receptors. However the pathway between muscarinic receptor activation and current inhibition is unknown. Using two structurally distinct inhibitors of the activation of MEK1 (mitogen activated protein (MAP) kinase kinase 1), PD 98059 and U 0126, we have shown that the MAP kinase signalling cascade does not appear to underlie muscarinic inhibition of IK(SO), recorded using whole-cell patch-clamp methods. Nevertheless, both PD 98059 and U 0126 caused an inhibition of IK(SO) when applied acutely with 30 microM of each compound producing around 50% inhibition of the current. In addition, U 0125, which is structurally related to U 0126 but has a much lower potency for inhibiting MEK1 activation, was also able to inhibit IK(SO) to a similar degree.Neither the inhibition by PD 98059 nor that by U 0126 was found to be voltage dependent. This was true whether the IK(SO) current was outward or inward. Block of IK(SO) by these two compounds may compromise interpretation of studies in intact neuronal preparations when they are used as MEK1 inhibitors.

Item Type: Article
DOI/Identification number: 10.1016/S0028-3908(01)00168-X
Subjects: Q Science > QP Physiology (Living systems)
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Alistair Mathie
Date Deposited: 09 Mar 2009 23:44 UTC
Last Modified: 16 Nov 2021 09:43 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/5691 (The current URI for this page, for reference purposes)

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