Loss of Cav1.3 Channels Reveals the Critical Role of L-Type and BK Channel Coupling in Pacemaking Mouse Adrenal Chromaffin Cells
Autor: | Emilio Carbone, Andrea Marcantoni, Joerg Striessnig, Valentina Carabelli, Satyajit Mahapatra, David Vandael, Martina J. Sinnegger-Brauns |
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Rok vydání: | 2010 |
Předmět: |
medicine.medical_specialty
BK channel Indoles Patch-Clamp Techniques Time Factors Calcium Channels L-Type Chromaffin Cells Biophysics Spider Venoms Biophysical Phenomena Membrane Potentials Cav1.3 Mice chemistry.chemical_compound Pacemaker potential Nifedipine BAPTA Internal medicine Potassium Channel Blockers medicine Animals Large-Conductance Calcium-Activated Potassium Channels Paxilline Egtazic Acid Cells Cultured Chelating Agents Mice Knockout Dose-Response Relationship Drug Ionophores biology General Neuroscience Afterhyperpolarization Articles 3-Pyridinecarboxylic acid 1 4-dihydro-2 6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)- Methyl ester Calcium Channel Blockers Electric Stimulation Coupling (electronics) Calcium Channel Agonists Endocrinology Gene Expression Regulation chemistry Adrenal Medulla Adrenal Cortex biology.protein medicine.drug |
Zdroj: | The Journal of Neuroscience. 30:491-504 |
ISSN: | 1529-2401 0270-6474 |
Popis: | We studied wild-type (WT) andCav1.3−/−mouse chromaffin cells (MCCs) with the aim to determine the isoform of L-type Ca2+channel (LTCC) and BK channels that underlie the pacemaker current controlling spontaneous firing. Most WT-MCCs (80%) were spontaneously active (1.5 Hz) and highly sensitive to nifedipine and BayK-8644 (1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-3-pyridinecarboxylic acid, methyl ester). Nifedipine blocked the firing, whereas BayK-8644 increased threefold the firing rate. The two dihydropyridines and the BK channel blocker paxilline altered the shape of action potentials (APs), suggesting close coupling of LTCCs to BK channels. WT-MCCs expressed equal fractions of functionally active Cav1.2 and Cav1.3 channels. Cav1.3 channel deficiency decreased the number of normally firing MCCs (30%; 2.0 Hz), suggesting a critical role of these channels on firing, which derived from their slow inactivation rate, sizeable activation at subthreshold potentials, and close coupling to fast inactivating BK channels as determined by using EGTA and BAPTA Ca2+buffering. By means of the action potential clamp, in TTX-treated WT-MCCs, we found that the interpulse pacemaker current was always net inward and dominated by LTCCs. Fast inactivating and non-inactivating BK currents sustained mainly the afterhyperpolarization of the short APs (2–3 ms) and only partially the pacemaker current during the long interspike (300–500 ms). Deletion of Cav1.3 channels reduced drastically the inward Ca2+current and the corresponding Ca2+-activated BK current during spikes. Our data highlight the role of Cav1.3, and to a minor degree of Cav1.2, as subthreshold pacemaker channels in MCCs and open new interesting features about their role in the control of firing and catecholamine secretion at rest and during sustained stimulations matching acute stress. |
Databáze: | OpenAIRE |
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