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Interaction of Ro 40-5967 and verapamil with the stably expressed alpha 1-subunit of the cardiac L-type calcium channel

The interaction of the nondihydropyridine calcium channel antagonist Ro 40-5967 with the stably expressed class C alpha 1-subunit of the cardiac L-type calcium channel was investigated and compared with that of verapamil by using the whole cell patch clamp configuration. Both compounds blocked the B...

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Bibliographic Details
Main Authors: Lacinova, Lubica (Author) , Welling, A. (Author) , Bosse, E. (Author) , Ruth, P. (Author) , Flockerzi, Veit (Author) , Hofmann, Franz (Author)
Format: Article (Journal)
Language:English
Published: July 1995
In: The journal of pharmacology and experimental therapeutics
Year: 1995, Volume: 274, Issue: 1, Pages: 54-63
ISSN:1521-0103
DOI:10.1016/S0022-3565(25)10679-4
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/S0022-3565(25)10679-4
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0022356525106794
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Author Notes:L. Lacinová, A. Welling, E. Bosse, P. Ruth, V. Flockerzi, F. Hofmann
Description
Summary:The interaction of the nondihydropyridine calcium channel antagonist Ro 40-5967 with the stably expressed class C alpha 1-subunit of the cardiac L-type calcium channel was investigated and compared with that of verapamil by using the whole cell patch clamp configuration. Both compounds blocked the Ba++ inward current. The IC50 values at a holding potential of -80 or -40 mV were 4.9 and 1.4 microM for Ro 40-5967 and 250 and 15.5 microM for verapamil. Both Ro 40-5967 and verapamil induced a partial tonic block at a holding potential of -80 mV. The block increased with high depolarization rates. Both Ro 40-5967 and verapamil shifted the steady-state inactivation curve by more than 20 mV to hyperpolarized membrane potentials and decreased the inactivation rate constant. The effect of Ro 40-5967, but not that of verapamil, was attenuated by intracellular dialysis with GTP gamma S. The affinity for verapamil was not affected by replacing Ba++ by Ca++, but was increased by the coexpression of the beta 3-subunit. These results indicate that both compounds interact with high affinity with the inactivated channel state, but may interact additionally with the open channel.
Item Description:Elektronische Reproduktion der Druck-Ausgabe 31. Januar 2025
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Physical Description:Online Resource
ISSN:1521-0103
DOI:10.1016/S0022-3565(25)10679-4

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