title: Reconstruction of the dihydropyridine site in a non-L-type calcium channel: the role of the IS6 segment.
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.
authors.affiliation: Institut für Pharmakologie und Toxikologie, TU München, Munich, Germany. lacinova@ipt.med.tu-muenchen.de
authors.forename: L
authors.initials: L
authors.lastname: Lacinová
authors.forename: N
authors.initials: N
authors.lastname: Klugbauer
authors.forename: M
authors.initials: M
authors.lastname: Hu
authors.forename: F
authors.initials: F
authors.lastname: Hofmann
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000737:chemistry*; D002460:Cell Line; D004095:Dihydropyridines / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D020128:Inhibitory Concentration 50; D017275:Isradipine / Q000494:pharmacology; D016296:Mutagenesis; D011993:Recombinant Fusion Proteins
chemical_list: D015220:Calcium Channels; D004095:Dihydropyridines; D011993:Recombinant Fusion Proteins; C038806:1,4-dihydropyridine; D017275:Isradipine