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

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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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Different firing patterns of spontaneously active RCCs and MCCs. a, b) Spontaneous AP traces recorded from two different RCCs displaying typical tonic irregular and tonic regular firing patterns, respectively. c) Representative trace of spontaneous AP trains fired in a burst-like mode recorded from a MCC. To the right are shown a single burst at an expanded time scale (grey window) and the overlap of consecutive APs within a burst. Numbers indicate the position/sequence in the burst (adapted from ref. [24]).
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Figure 1: Different firing patterns of spontaneously active RCCs and MCCs. a, b) Spontaneous AP traces recorded from two different RCCs displaying typical tonic irregular and tonic regular firing patterns, respectively. c) Representative trace of spontaneous AP trains fired in a burst-like mode recorded from a MCC. To the right are shown a single burst at an expanded time scale (grey window) and the overlap of consecutive APs within a burst. Numbers indicate the position/sequence in the burst (adapted from ref. [24]).

Mentions: Spontaneous firing is rather variable in CCs regardless of whether the cells are isolated [9-11, 16, 18-20, 24] or in slices of the adrenal gland [21-23]. In many CCs the firing is “tonic irregular”, i.e., spikes occur at variable frequency (Fig. 1a). In mouse CCs (MCCs), the degree of regularity is negatively correlated with spike frequencies recorded at rest. Fast spiking cells are typically more regular and display “tonic regular” firings (Fig. 1b).


Ca v 1.3 Channels as Key Regulators of Neuron-Like Firings and Catecholamine Release in Chromaffin Cells
Different firing patterns of spontaneously active RCCs and MCCs. a, b) Spontaneous AP traces recorded from two different RCCs displaying typical tonic irregular and tonic regular firing patterns, respectively. c) Representative trace of spontaneous AP trains fired in a burst-like mode recorded from a MCC. To the right are shown a single burst at an expanded time scale (grey window) and the overlap of consecutive APs within a burst. Numbers indicate the position/sequence in the burst (adapted from ref. [24]).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384372&req=5

Figure 1: Different firing patterns of spontaneously active RCCs and MCCs. a, b) Spontaneous AP traces recorded from two different RCCs displaying typical tonic irregular and tonic regular firing patterns, respectively. c) Representative trace of spontaneous AP trains fired in a burst-like mode recorded from a MCC. To the right are shown a single burst at an expanded time scale (grey window) and the overlap of consecutive APs within a burst. Numbers indicate the position/sequence in the burst (adapted from ref. [24]).
Mentions: Spontaneous firing is rather variable in CCs regardless of whether the cells are isolated [9-11, 16, 18-20, 24] or in slices of the adrenal gland [21-23]. In many CCs the firing is “tonic irregular”, i.e., spikes occur at variable frequency (Fig. 1a). In mouse CCs (MCCs), the degree of regularity is negatively correlated with spike frequencies recorded at rest. Fast spiking cells are typically more regular and display “tonic regular” firings (Fig. 1b).

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