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ERG K+ channel blockade enhances firing and epinephrine secretion in rat chromaffin cells: the missing link to LQT2-related sudden death?
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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, K-ATP, and K-Ca 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.
|Title:||ERG K+ channel blockade enhances firing and epinephrine secretion in rat chromaffin cells: the missing link to LQT2-related sudden death?|
|Keywords:||catecholamine release, eag superfamily, erg gene, arrhythmia, adrenal medulla, LONG-QT SYNDROME, CATECHOLAMINE RELEASE, POTASSIUM CHANNEL, CARDIAC-ARRHYTHMIA, I-KR, VENTRICULAR MYOCYTES, ADRENAL-GLAND, HERG, IDENTIFICATION, MUTATIONS|
|UCL classification:||UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Child Health
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