Action potential (AP) firing in mouse chromaffin cells (MCCs) is mainly sustained by Cav1.3 L-type channels that drive BK and SK currents and regulate the pacemaking cycle. As secretory units, CCs optimally recruit Ca2+ channels when stimulated, a process potentially dependent on the modulation of the AP waveform. Our previous work has shown that a critical determinant of AP shape is voltage-gated sodium channel (Nav) channel availability. Here, we studied the contribution of Nav channels to firing patterns and AP shapes at rest (−50 mV) anduponstimulation (−40 mV). Using quantitative RT-PCR and immunoblotting, we show that MCCs mainly express tetrodotoxin (TTX)-sensitive, fast-inactivating Nav1.3 and Nav1.7 channels that carry little or no Na+ current during slow ramp depolarizations. Time constants and the percentage of recovery fromfast inactivation and slowentry into closed-state inactivation are similar to that of brain Nav1.3 and Nav1.7 channels. The fraction of available Nav channels is reduced by half after 10 mV depolarization from−50 to−40 mV. This leads to low amplitude spikes and a reduction in repolarizing K+ currents inverting the net current from outward to inward during the after-hyperpolarization. When Nav channel availability is reduced by up to 20% of total, either by TTX block or steady depolarization, a switch from tonic to burst firing is observed. The spontaneous occurrence of high frequency bursts is rare under control conditions (14% of cells) but leads to major Ca2+-entry and increased catecholamine release. Thus, Nav1.3/Nav1.7 channel availability sets the AP shape, burst-firing initiation and regulates catecholamine secretion inMCCs. Nav channel inactivation becomes important during periods of high activity,mimicking stress responses.

Reduced availability of voltage-gated sodium channels by depolarization or blockade by tetrodotoxin boosts burst firing and catecholamine release in mouse chromaffin cells

VANDAEL, DAVID HENRI FRANCOIS;OTTAVIANI, MATTEO MARIA;ALLIO, ARIANNA;CARABELLI, Valentina;CARBONE, Emilio
2015

Abstract

Action potential (AP) firing in mouse chromaffin cells (MCCs) is mainly sustained by Cav1.3 L-type channels that drive BK and SK currents and regulate the pacemaking cycle. As secretory units, CCs optimally recruit Ca2+ channels when stimulated, a process potentially dependent on the modulation of the AP waveform. Our previous work has shown that a critical determinant of AP shape is voltage-gated sodium channel (Nav) channel availability. Here, we studied the contribution of Nav channels to firing patterns and AP shapes at rest (−50 mV) anduponstimulation (−40 mV). Using quantitative RT-PCR and immunoblotting, we show that MCCs mainly express tetrodotoxin (TTX)-sensitive, fast-inactivating Nav1.3 and Nav1.7 channels that carry little or no Na+ current during slow ramp depolarizations. Time constants and the percentage of recovery fromfast inactivation and slowentry into closed-state inactivation are similar to that of brain Nav1.3 and Nav1.7 channels. The fraction of available Nav channels is reduced by half after 10 mV depolarization from−50 to−40 mV. This leads to low amplitude spikes and a reduction in repolarizing K+ currents inverting the net current from outward to inward during the after-hyperpolarization. When Nav channel availability is reduced by up to 20% of total, either by TTX block or steady depolarization, a switch from tonic to burst firing is observed. The spontaneous occurrence of high frequency bursts is rare under control conditions (14% of cells) but leads to major Ca2+-entry and increased catecholamine release. Thus, Nav1.3/Nav1.7 channel availability sets the AP shape, burst-firing initiation and regulates catecholamine secretion inMCCs. Nav channel inactivation becomes important during periods of high activity,mimicking stress responses.
THE JOURNAL OF PHYSIOLOGY
593
4
905
927
https://pubmed.ncbi.nlm.nih.gov/25620605/
Canali del Na voltaggio dipendenti; Canali del calcio di tipo L; canali BK; secrezione calcio-dipendente; Fisiologia e Biofisica delle cellule cromaffini; potenziali d'azione spontanei; Tone bursts
David H. F. Vandael;Matteo M. Ottaviani;Christian Legros;Claudie Lefort;Nathalie C. Guérineau;Arianna Allio;Valentina Carabelli;Emilio Carbone
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/154812
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