Q-type Ca2+ channels are located closer to secretory sites than L-type channels: functional evidence in chromaffin cells |
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Authors: | Baldomero Lara Luis Gandía Rafael Martínez-Sierra Andrés Torres A G García |
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Institution: | (1) Departamento de Farmacología, Facultad de Medicina, Servicio de Farmacología Clínica, Hospital Reina Sofía, Universidad de Córdoba, Avda. Menéndez Pidal, s/n, E-14071 Córdoba, Spain, ES;(2) Departamento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Arzobispo Morcillo, 4, E-28029, Madrid, Spain, ES;(3) Servicio de Farmacología Clínica e Instituto de Gerontología, Hospital de la Princesa, Diego de León, 62, E-28006, Madrid, Spain, ES |
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Abstract: | This study uses a new strategy to investigate the hypothesis that, of the various Ca2+ channels expressed by a neurosecretory cell, a given channel subtype is coupled more tightly to the exocytotic apparatus
than others. The approach is based on the prediction that the degree of inhibition of the secretory response by various Ca2+ channel blockers will differ at low (0.5 mM) and high (5 mM) extracellular Ca2+ concentrations (Ca2+]o). So, at low Ca2+]o the K+-evoked catecholamine release from superfused bovine chromaffin cells was depressed 60–70% by 2 μM ω-agatoxin IVA (P/Q-type
Ca2+ channel blockade), by 3 μM ω-conotoxin MVIIC (N/P/Q-type Ca2+ channel blockade), or by 3 μM lubeluzole (N/P/Q-type Ca2+ channel blockade); in high Ca2+]o these blockers inhibited the responses by only 20–35%. At 1–3 μM ω-conotoxin GVIA (N-type Ca2+ channel blockade) or 3 μM furnidipine (L-type Ca2+ channel blockade), secretion was inhibited by 30 and 50%, respectively; such inhibitory effects were similar in low or high
Ca2+]o. Combined furnidipine plus ω-conotoxin MVIIC, ω-agatoxin IVA or ω-conotoxin GVIA exhibited additive blocking effects at
both Ca2+ concentrations. The results suggest that Q-type Ca2+ channels are coupled more tightly to exocytotic active sites, as compared to L-type channels. This hypothesis if founded
in the fact that external Ca2+ that enters the cell through a Ca2+ channel located near to chromaffin vesicles will saturate the K+ secretory response at both Ca2+]o, i.e. 0.5 mM and 5 mM. In contrast, Ca2+ ions entering through more distant channels will be sequestered by intracellular buffers and, thus, will not saturate the
secretory machinery at lower Ca2+]o.
Received: 23 September 1997 / Received after revision: 29 October 1997 / Accepted: 30 October 1997 |
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Keywords: | Ca2+ channels Exocytosis Chromaffin cells Catecholamine release ω -toxins Furnidipine Lubeluzole |
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