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Ca v 1.3 Channels as Key Regulators of Neuron-Like Firings and Catecholamine Release in Chromaffin Cells

View Article: PubMed Central - PubMed

ABSTRACT

Neuronal and neuroendocrine L-type calcium channels (Cav1.2, Cav1.3) open readily at relatively low membrane potentials and allow Ca2+ to enter the cells near resting potentials. In this way, Cav1.2 and Cav1.3 shape the action potential waveform, contribute to gene expression, synaptic plasticity, neuronal differentiation, hormone secretion and pacemaker activity. In the chromaffin cells (CCs) of the adrenal medulla, Cav1.3 is highly expressed and is shown to support most of the pacemaking current that sustains action potential (AP) firings and part of the catecholamine secretion. Cav1.3 forms Ca2+-nanodomains with the fast inactivating BK channels and drives the resting SK currents. These latter set the inter-spike interval duration between consecutive spikes during spontaneous firing and the rate of spike adaptation during sustained depolarizations. Cav1.3 plays also a primary role in the switch from “tonic” to “burst” firing that occurs in mouse CCs when either the availability of voltage-gated Na channels (Nav) is reduced or the β2 subunit featuring the fast inactivating BK channels is deleted. Here, we discuss the functional role of these “neuron-like” firing modes in CCs and how Cav1.3 contributes to them. The open issue is to understand how these novel firing patterns are adapted to regulate the quantity of circulating catecholamines during resting condition or in response to acute and chronic stress.

No MeSH data available.


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Burst firing associated with Nav channel block boosts MCC exocytosis. a) Experimental arrangement to record catecholamine secretion using a carbon fibre microelectrode (CFE) from a current-clamped MCC. The cell is constantly depolarized to evoke an AP train (Vm) by passing a constant current (i) through the glass pipette using a square pulse voltage command (Vcmd). The quantal release of adrenaline and noradrenaline is detected in forms of amperometric currents by the CFE (Iamp) placed very close to the CC. b) Top, example of combined recording of APs (black traces) and amperometric currents (grey traces) by CFE amperometry in control. Middle, combined recording of AP bursts and amperometric events during TTX application to the same cell of the top. Bottom, overlap of cumulative secretion plots obtained by integrating the amperometric recordings shown in a and b for control (black trace) and TTX application (grey trace) (adapted from ref. [24]).
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Figure 7: Burst firing associated with Nav channel block boosts MCC exocytosis. a) Experimental arrangement to record catecholamine secretion using a carbon fibre microelectrode (CFE) from a current-clamped MCC. The cell is constantly depolarized to evoke an AP train (Vm) by passing a constant current (i) through the glass pipette using a square pulse voltage command (Vcmd). The quantal release of adrenaline and noradrenaline is detected in forms of amperometric currents by the CFE (Iamp) placed very close to the CC. b) Top, example of combined recording of APs (black traces) and amperometric currents (grey traces) by CFE amperometry in control. Middle, combined recording of AP bursts and amperometric events during TTX application to the same cell of the top. Bottom, overlap of cumulative secretion plots obtained by integrating the amperometric recordings shown in a and b for control (black trace) and TTX application (grey trace) (adapted from ref. [24]).

Mentions: Figure 7 shows that this indeed is the case if current-clamped MCCs are first hyperpolarized to stop their spontaneous activity and prevent Ca2+ accumulation at the onset of the recording. Control cells and cells pre-treated with TTX are then stimulated for 40 s with a constant depolarizing pulse to induce secretion. The fast quantal release of catecholamines revealed with carbon fibre amperometry [11, 61] (Fig. 7a) shows clearly that the increased AP frequency during bursts in the presence of TTX enhances significantly the quantity of released catecholamines (Fig. 7b, bottom). Thus, block of Nav channels with TTX to induce burst firing paradoxically boosts Ca2+-entry and release of catecholamines. Although not shown, it is likely that most of the exocytosis is sustained by Cav1.3 since is the dominant pacemaking channel supporting prolonged depolarizations in MCCs.


Ca v 1.3 Channels as Key Regulators of Neuron-Like Firings and Catecholamine Release in Chromaffin Cells
Burst firing associated with Nav channel block boosts MCC exocytosis. a) Experimental arrangement to record catecholamine secretion using a carbon fibre microelectrode (CFE) from a current-clamped MCC. The cell is constantly depolarized to evoke an AP train (Vm) by passing a constant current (i) through the glass pipette using a square pulse voltage command (Vcmd). The quantal release of adrenaline and noradrenaline is detected in forms of amperometric currents by the CFE (Iamp) placed very close to the CC. b) Top, example of combined recording of APs (black traces) and amperometric currents (grey traces) by CFE amperometry in control. Middle, combined recording of AP bursts and amperometric events during TTX application to the same cell of the top. Bottom, overlap of cumulative secretion plots obtained by integrating the amperometric recordings shown in a and b for control (black trace) and TTX application (grey trace) (adapted from ref. [24]).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 7: Burst firing associated with Nav channel block boosts MCC exocytosis. a) Experimental arrangement to record catecholamine secretion using a carbon fibre microelectrode (CFE) from a current-clamped MCC. The cell is constantly depolarized to evoke an AP train (Vm) by passing a constant current (i) through the glass pipette using a square pulse voltage command (Vcmd). The quantal release of adrenaline and noradrenaline is detected in forms of amperometric currents by the CFE (Iamp) placed very close to the CC. b) Top, example of combined recording of APs (black traces) and amperometric currents (grey traces) by CFE amperometry in control. Middle, combined recording of AP bursts and amperometric events during TTX application to the same cell of the top. Bottom, overlap of cumulative secretion plots obtained by integrating the amperometric recordings shown in a and b for control (black trace) and TTX application (grey trace) (adapted from ref. [24]).
Mentions: Figure 7 shows that this indeed is the case if current-clamped MCCs are first hyperpolarized to stop their spontaneous activity and prevent Ca2+ accumulation at the onset of the recording. Control cells and cells pre-treated with TTX are then stimulated for 40 s with a constant depolarizing pulse to induce secretion. The fast quantal release of catecholamines revealed with carbon fibre amperometry [11, 61] (Fig. 7a) shows clearly that the increased AP frequency during bursts in the presence of TTX enhances significantly the quantity of released catecholamines (Fig. 7b, bottom). Thus, block of Nav channels with TTX to induce burst firing paradoxically boosts Ca2+-entry and release of catecholamines. Although not shown, it is likely that most of the exocytosis is sustained by Cav1.3 since is the dominant pacemaking channel supporting prolonged depolarizations in MCCs.

View Article: PubMed Central - PubMed

ABSTRACT

Neuronal and neuroendocrine L-type calcium channels (Cav1.2, Cav1.3) open readily at relatively low membrane potentials and allow Ca2+ to enter the cells near resting potentials. In this way, Cav1.2 and Cav1.3 shape the action potential waveform, contribute to gene expression, synaptic plasticity, neuronal differentiation, hormone secretion and pacemaker activity. In the chromaffin cells (CCs) of the adrenal medulla, Cav1.3 is highly expressed and is shown to support most of the pacemaking current that sustains action potential (AP) firings and part of the catecholamine secretion. Cav1.3 forms Ca2+-nanodomains with the fast inactivating BK channels and drives the resting SK currents. These latter set the inter-spike interval duration between consecutive spikes during spontaneous firing and the rate of spike adaptation during sustained depolarizations. Cav1.3 plays also a primary role in the switch from “tonic” to “burst” firing that occurs in mouse CCs when either the availability of voltage-gated Na channels (Nav) is reduced or the β2 subunit featuring the fast inactivating BK channels is deleted. Here, we discuss the functional role of these “neuron-like” firing modes in CCs and how Cav1.3 contributes to them. The open issue is to understand how these novel firing patterns are adapted to regulate the quantity of circulating catecholamines during resting condition or in response to acute and chronic stress.

No MeSH data available.


Related in: MedlinePlus