Premium
The selective action of quinacrine on high‐threshold calcium channels in rat hippocampal cells
Author(s) -
Mironov S.L.,
Lux H.D.
Publication year - 1992
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.1476-5381.1992.tb14405.x
Subject(s) - tetrodotoxin , chemistry , depolarization , biophysics , sodium channel , membrane potential , voltage dependent calcium channel , patch clamp , channel blocker , calcium , biochemistry , receptor , sodium , biology , organic chemistry
1 The whole‐cell patch‐clamp technique has been used to examine Ca channel currents carried by Ba ( I Ba ) in rat hippocampal neurones. 2 Quinacrine selectivity decreased the high‐threshold current activated by membrane depolarization from a holding potential of −70 mV. Neither the low‐threshold Ca channel current nor the fast tetrodotoxin (TTX)‐sensitive sodium current were affected by quinacrine. 3 Bath application of quinacrine caused a dose‐dependent reduction of the peak amplitude of I Ba . This effect was fast, voltage‐independent, reversible and had a K d of 30 ± 5 μ m . 4 The quinacrine‐induced block did not change the time‐course and the voltage dependence of I Ba activation and deactivation. The inhibition revealed no use‐dependence, ruling out an open channel block by quinacrine. 5 p ‐Bromophenacyl bromide had no effect on I Ba suggesting the lack of involvement of phospholipase A 2 in the action of quinacrine. In addition, the quinacrine‐induced block was not related to the calmodulin pathway and internal quinacrine did not affect the peak amplitude of I Ba . 6 The effect of quinacrine on the amplitude of I Ba was dependent of the external pH, and suggested that only the single‐protonated form of the drug can bind to the channel receptor with a K d of 3 μ m . Quinacrine and other substituted acridines can thus be useful for pharmacological and structure‐activity studies of Ca channels.