Reconstruction of the dihydropyridine site in a non-L-type calcium channel: the role of the IS6 segment. |
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Authors: | L Lacinová N Klugbauer M Hu F Hofmann |
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Institution: | Institut für Pharmakologie und Toxikologie, TU München, Munich, Germany. lacinova@ipt.med.tu-muenchen.de |
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Abstract: | Mutations of eight to nine amino acids of IIIS5, IIIS6 and IVS6 segments were shown to reconstruct the dihydropyridine (DHP) interaction site in the non-L-type alpha1E or alpha1A calcium channels. The reconstructed site enabled enantiomer-selective inhibition and activation of the expressed chimeras by DHPs but failed to transfer voltage dependence of the current inhibition. Here we show that transfer of four non-conserved amino acids from the IS6 segment to the DHP-sensitive alpha1E chimera increased the inhibition by (+)isradipine at the hyperpolarized membrane potential of -100 mV and enhanced the voltage-dependent block. |
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