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

• Verfasst von: Lacinova, Lubica [VerfasserIn]
• Verfasst von: Welling, A. [VerfasserIn]
• Verfasst von: Bosse, E. [VerfasserIn]
• Verfasst von: Ruth, P. [VerfasserIn]
• Verfasst von: Flockerzi, Veit [VerfasserIn]
• Verfasst von: Hofmann, Franz [VerfasserIn]
• Titel: Interaction of Ro 40-5967 and verapamil with the stably expressed alpha 1-subunit of the cardiac L-type calcium channel
• Verf.angabe: L. Lacinová, A. Welling, E. Bosse, P. Ruth, V. Flockerzi, F. Hofmann
• E-Jahr: 1995
• Jahr: July 1995
• Umfang: 10 S.
• Fussnoten: Elektronische Reproduktion der Druck-Ausgabe 31. Januar 2025 ; Gesehen am 17.02.2025
• Titel Quelle: Enthalten in: The journal of pharmacology and experimental therapeutics
• Ort Quelle: Bethesda, Md. : ASPET, 1909
• Jahr Quelle: 1995
• Band/Heft Quelle: 274(1995), 1, Seite 54-63
• ISSN Quelle: 1521-0103
• DOI: doi:10.1016/S0022-3565(25)10679-4
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1917391420

Abstract

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.