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Effects on K + currents in rat cerebellar granule neurones of a membrane‐permeable analogue of the calcium chelator BAPTA
Author(s) -
Watkins Christopher S.,
Mathie Alistair
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15603.x
Subject(s) - bapta , tetraethylammonium , chemistry , biophysics , calcium , biochemistry , biology , extracellular , potassium , organic chemistry
1 . Whole cell recordings of voltage‐activated K + currents were made with the amphotericin B perforated patch technique from cerebellar granule (CG) neurones of 6–8 days rats that had been in culture for 1 to 16 days. By use of appropriate voltage protocols, the effects of the membrane‐permeant form of BAPTA, 1,2‐ bis ‐(2‐amino‐phenoxy)ethane‐ N,N,N′,N′ ‐tetraacetic acid acetoxymethyl ester (BAPTA‐AM), on the transient A current ( I KA ), the delayed rectifier current ( I Kv ) and a standing outward current ( I Kso ) were investigated. 2 . Bath application of 25 μ m BAPTA‐AM inhibited both I Kv and I Kso in cultured neurones, but did not seem to affect I KA . Neither 25 μ m BAPTA (free acid) nor 25 μ m ethylenediaminetetraacetic acid acetoxymethyl ester (EDTA‐AM) had any significant effect on the magnitude of I Kso . Similarly in short‐term (1–2 days) cultured CG neurones I Kv , but not I KA , was inhibited by 25 μ m BAPTA‐AM. 3 . BAPTA‐AM (2.5 μ m ) reduced I Kv in short‐term culture CG neurones, with further inhibition being seen when the perfusate was changed to one containing 25 μ m BAPTA‐AM. 4 . Tetraethylammonium ions (TEA) (10 mM) reversibly inhibited I Kv in these cells with a similar rate of block of I Kv to that induced by 25 μ m BAPTA‐AM. 5 . The degree of inhibition of I Kv by 25 μ m BAPTA‐AM was both time‐ and voltage‐dependent, in contrast to the inhibition of this current by TEA. 6 . These data indicate that BAPTA‐AM reduces K + currents in cerebellar granule neurones and that this inhibition cannot be explained in terms of intracellular Ca 2+ chelation, but is a direct effect on the underlying channels.

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