Roles of Na+, Ca2+, and K+ channels in the generation of repetitive firing and rhythmic bursting in adrenal chromaffin cells

Abstract

Adrenal chromaffin cells (CCs) are the main source of circulating catecholamines (CAs) that regulate the body response to stress. Release of CAs is controlled neurogenically by the activity of preganglionic sympathetic neurons through trains of action potentials (APs). APs in CCs are generated by robust depolarization following the activation of nicotinic and muscarinic receptors that are highly expressed in CCs. Bovine, rat, mouse, and human CCs also express a composite array of Na, K, and Ca channels that regulate the resting potential, shape the APs, and set the frequency of AP trains. AP trains of increasing frequency induce enhanced release of CAs. If the primary role of CCs is simply to relay preganglionic nerve commands to CA secretion, why should they express such a diverse set of ion channels? An answer to this comes from recent observations that, like in neurons, CCs undergo complex firing patterns of APs suggesting the existence of an intrinsic CC excitability (non-neurogenically controlled). Recent work has shown that CCs undergo occasional or persistent burst firing elicited by altered physiological conditions or deletion of pore-regulating auxiliary subunits. In this review, we aim to give a rationale to the role of the many ion channel types regulating CC excitability. We will first describe their functional properties and then analyze how they contribute to pacemaking, AP shape, and burst waveforms. We will also furnish clear indications on missing ion conductances that may be involved in pacemaking and highlight the contribution of the crucial channels involved in burst firing.

Impaired chromaffin cell excitability and exocytosis in autistic Timothy syndrome TS2‐neo mouse rescued by L‐type calcium channel blockers

“… b ; Lingle et al . ). We found that peak Nav currents during step depolarization to −10 or 0 mV in 2 mM Ca 2+ had variable amplitudes with a clear trend to decrease in TS2‐mutated MCCs (mean values 1.25 vs .…”

“…; Lingle et al . ). Here, we studied how the TS2‐neo mutation alters mouse chromaffin cell (MCC) function.…”

Ca2+‐independent and voltage‐dependent exocytosis in mouse chromaffin cells

“…Initial works using extracellular electrodes estimated very low spontaneous frequencies in rat chromaffin cells, between 0.1 and 0.4 Hz, and more recently with perforated patch other authors obtained a frequency of 0.2 Hz in bovine cells . However, in the recent years spontaneous frequencies up to 1.5 Hz were estimated in mouse chromaffin cells . Our results show that CIVDE would be significant within the limits of this frequency variability.…”

“…In contrast, the application of trains at 2 Hz provoked approximately 50% decrease (open circles), and 5 Hz induced almost the complete depression of synchronous exocytosis (black diamonds). These results indicate that AP ls triggers CIVDE only at low frequencies, below 2 Hz, what includes the range of most commonly estimated frequencies in chromaffin cells basal conditions …”

Voltage-Gated Na+ Channels are Modulated by Glucose and Involved in Regulating Cellular Insulin Content of INS-1 Cells

“…Large rapid depolarization results in opening of the Na + channel and inward Na + current. Activation, deactivation, and inactivation in VGSCs link various physiological processes to electrical activity by controlling the action potentials in nerve, muscle and other excitable cells [3], such as adrenal chromaffin cells [7]. VGSCs mediate the influx of Na + into the cytosol of cells in response to local membrane depolarization, thereby generating the upstroke phase of an action potential [3].…”