Functional, electrophysiological and molecular docking analysis of the modulation of Cav 1.2 channels in rat vascular myocytes by murrayafoline A
| Autor: | Saponara, S, Durante, M, Spiga, O, Mugnai, P, Sgaragli, G, Huong, TT, Khanh, PN, Son, NT, Cuong, NM, Fusi, F |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Calcium Channels L-Type Dose-Response Relationship Drug Cav1.2 channel Myocytes Smooth Muscle Carbazoles patch-clamp Research Papers Muscle Smooth Vascular Protein Structure Secondary Electrophysiological Phenomena Protein Structure Tertiary Rats Molecular Docking Simulation Alkaloids Organ Culture Techniques vascular smooth muscle docking Animals Endothelium Vascular murrayafoline A Rats Wistar Cav1.2 channel murrayafoline A patch-clamp vascular smooth muscle docking |
| Popis: | The carbazole alkaloid murrayafoline A (MuA) enhances contractility and the Ca(2+) currents carried by the Cav 1.2 channels [ICa1.2 ] of rat cardiomyocytes. As only few drugs stimulate ICa1.2 , this study was designed to analyse the effects of MuA on vascular Cav 1.2 channels.Vascular activity was assessed on rat aorta rings mounted in organ baths. Cav 1.2 Ba(2+) current [IBa1.2 ] was recorded in single rat aorta and tail artery myocytes by the patch-clamp technique. Docking at a 3D model of the rat, α1c central pore subunit of the Cav 1.2 channel was simulated in silico.In rat aorta rings MuA, at concentrations ≤14.2 μM, increased 30 mM K(+) -induced tone and shifted the concentration-response curve to K(+) to the left. Conversely, at concentrations14.2 μM, it relaxed high K(+) depolarized rings and antagonized Bay K 8644-induced contraction. In single myocytes, MuA stimulated IBa1.2 in a concentration-dependent, bell-shaped manner; stimulation was stable, incompletely reversible upon drug washout and accompanied by a leftward shift of the voltage-dependent activation curve. MuA docked at the α1C subunit central pore differently from nifedipine and Bay K 8644, although apparently interacting with the same amino acids of the pocket. Neither Bay K 8644-induced stimulation nor nifedipine-induced block of IBa1.2 was modified by MuA.Murrayafoline A is a naturally occurring vasoactive agent able to modulate Cav 1.2 channels and dock at the α1C subunit central pore in a manner that differed from that of dihydropyridines. |
| Databáze: | OpenAIRE |
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