Low pH inf o boosts burst firing and catecholamine release by blocking TASK-1 and BK channels while preserving Cav1 channels in mouse chromaffin cells

L. Guarina, D.H. Vandael, V. Carabelli, E. Carbone, Journal of Physiology 595 (2017) 2587–2609.

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Journal Article | Published | English
Author
Guarina, Laura; Vandael, David HIST Austria ; Carabelli, Valentina; Carbone, Emilio
Abstract
Mouse chromaffin cells (MCCs) generate action potential (AP) firing that regulates the Ca2+‐dependent release of catecholamines (CAs). Recent findings indicate that MCCs possess a variety of spontaneous firing modes that span from the common ‘tonic‐irregular’ to the less frequent ‘burst’ firing. This latter is evident in a small fraction of MCCs but occurs regularly when Nav1.3/1.7 channels are made less available or when the Slo1β2‐subunit responsible for BK channel inactivation is deleted. Burst firing causes large increases of Ca2+‐entry and potentiates CA release by ∼3.5‐fold and thus may be a key mechanism for regulating MCC function. With the aim to uncover a physiological role for burst‐firing we investigated the effects of acidosis on MCC activity. Lowering the extracellular pH (pHo) from 7.4 to 7.0 and 6.6 induces cell depolarizations of 10–15 mV that generate repeated bursts. Bursts at pHo 6.6 lasted ∼330 ms, occurred at 1–2 Hz and caused an ∼7‐fold increase of CA cumulative release. Burst firing originates from the inhibition of the pH‐sensitive TASK‐1/TASK‐3 channels and from a 40% BK channel conductance reduction at pHo 7.0. The same pHo had little or no effect on Nav, Cav, Kv and SK channels that support AP firing in MCCs. Burst firing of pHo 6.6 could be mimicked by mixtures of the TASK‐1 blocker A1899 (300 nm) and BK blocker paxilline (300 nm) and could be prevented by blocking L‐type channels by adding 3 μm nifedipine. Mixtures of the two blockers raised cumulative CA‐secretion even more than low pHo (∼12‐fold), showing that the action of protons on vesicle release is mainly a result of the ionic conductance changes that increase Ca2+‐entry during bursts. Our data provide direct evidence suggesting that MCCs respond to low pHo with sustained depolarization, burst firing and enhanced CA‐secretion, thus mimicking the physiological response of CCs to acute acidosis and hyperkalaemia generated during heavy exercise and muscle fatigue.
Publishing Year
Date Published
2017-04-15
Journal Title
Journal of Physiology
Volume
595
Issue
8
Page
2587 - 2609
IST-REx-ID

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Guarina L, Vandael DH, Carabelli V, Carbone E. Low pH inf o boosts burst firing and catecholamine release by blocking TASK-1 and BK channels while preserving Cav1 channels in mouse chromaffin cells. Journal of Physiology. 2017;595(8):2587-2609. doi:10.1113/JP273735
Guarina, L., Vandael, D. H., Carabelli, V., & Carbone, E. (2017). Low pH inf o boosts burst firing and catecholamine release by blocking TASK-1 and BK channels while preserving Cav1 channels in mouse chromaffin cells. Journal of Physiology. Wiley-Blackwell. https://doi.org/10.1113/JP273735
Guarina, Laura, David H Vandael, Valentina Carabelli, and Emilio Carbone. “Low PH Inf o Boosts Burst Firing and Catecholamine Release by Blocking TASK-1 and BK Channels While Preserving Cav1 Channels in Mouse Chromaffin Cells.” Journal of Physiology. Wiley-Blackwell, 2017. https://doi.org/10.1113/JP273735.
L. Guarina, D. H. Vandael, V. Carabelli, and E. Carbone, “Low pH inf o boosts burst firing and catecholamine release by blocking TASK-1 and BK channels while preserving Cav1 channels in mouse chromaffin cells,” Journal of Physiology, vol. 595, no. 8. Wiley-Blackwell, pp. 2587–2609, 2017.
Guarina L, Vandael DH, Carabelli V, Carbone E. 2017. Low pH inf o boosts burst firing and catecholamine release by blocking TASK-1 and BK channels while preserving Cav1 channels in mouse chromaffin cells. Journal of Physiology. 595(8), 2587–2609.
Guarina, Laura, et al. “Low PH Inf o Boosts Burst Firing and Catecholamine Release by Blocking TASK-1 and BK Channels While Preserving Cav1 Channels in Mouse Chromaffin Cells.” Journal of Physiology, vol. 595, no. 8, Wiley-Blackwell, 2017, pp. 2587–609, doi:10.1113/JP273735.

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