ERG K⁺channel blockade enhances firing and epinephrine secretion in rat chromaffin cells: the missing link to LQT2‐related sudden death?

Abstract

The ether-a-go-go-related genes (erg) are expressed in tissues other than heart and brain, in which human erg (HERG) K+ channels are known to regulate the repolarization of heart action potentials and neuronal spike-frequency accommodation. We provide evidence that erg1 transcripts and ERG proteins are present in rat chromaffin cells in which we could isolate a K+ current that was biophysically and pharmacologically similar to the ERG current. Firing frequency and catecholamine release were analyzed at the single-cell level by means of perforated patch-clamp and carbon fiber electrochemical detection. It was found that the blocking of ERG, KATP, and KCa channels led to hyperexcitability and an increase in catecholamine release. Combined immunocytochemical experiments with antibodies directed against phenylethanolamine N-methyltransferase and ERG channels suggested expression of these channels in epinephrine- but not in norepinephrine-containing cells. It is concluded that, in addition to being crucial in regulating the QT period in the heart, ERG channels play a role in modulating epinephrine, a fundamental neurotransmitter shaping cardiac function. This finding suggests that the sudden death phenotype associated with LQT2 syndrome mutations may be the result of an emotionally triggered increase in epinephrine in a long-QT running heart.

CaV1.3 as pacemaker channels in adrenal chromaffin cells: Specific role on exo- and endocytosis?

“…Bovine, rat, mouse and human adrenal chromaffin cells fire spontaneously when cultured in vitro 6,20,[30][31][32][33][34][35][36][37][38][39] or maintained in slices of the adrenal gland. 40,41 The percentage of firing chromaffin cells varies considerably (from 20 to 80%) depending review review catecholamines.…”

“…1) match those intracellularly recorded in perforated-patches. 37,38 Given that chromaffin cells are contacted by multiple cholinergic innervations that effectively control their activity by splanchnic nerve discharges, an unsolved question is why in vivo adrenal chromaffin cells should possess spontaneous AP activity. A possible explanation could be that chromaffin cells are packed together and electrically coupled by gap-junctions 41,43 to form groups of cells that synchronously release the content of secretory granules in nearby blood capillaries.…”

Resurgent Current and Voltage Sensor Trapping Enhanced Activation by a β-Scorpion Toxin Solely in Nav1.6 Channel

“…In order to test the Na v 1.7 channels, we used primary cultures of rat chromaffin cells (see Ref. 21 for details), since the selective presence of this channel alone is well documented (22) …”

“…Patch Clamp Recordings and Data Analysis-The currents were recorded at room temperature using the MultiClamp 700A (Axon Instruments) as previously described (21); pipette resistance was about 1.3-2.1 megaohms; cell capacitance and series resistance errors were carefully (85-90%) compensated for before each run of the voltage clamp protocol in order to reduce voltage errors to less than 5% of the protocol pulse. The P/N leak procedure was routinely used.…”

hERG1 channels are overexpressed in glioblastoma multiforme and modulate VEGF secretion in glioblastoma cell lines

“…This finding prompted us to investigate how hERG1 expression may represent a selective advantage to glial tumour cells. Due to the significance of angiogenic factor secretion in conferring high malignancy to gliomas, and since several studies indicate a role for hERG currents (I hERG ) in neuroendocrine secretion Bauer et al, 2003;Gullo et al, 2003), we sought a functional link between hERG1 activity and the secretion of angiogenic factors, such as VEGF.…”