Spontaneous and CRH-Induced Excitability and Calcium Signaling in Mice Corticotrophs Involves Sodium, Calcium, and Cation-Conducting Channels

Endocrinology
Hana ZemkovaStanko S Stojilkovic

Abstract

Transgenic mice expressing the tdimer2(12) form of Discosoma red fluorescent protein under control of the proopiomelanocortin gene's regulatory elements are a useful model for studying corticotrophs. Using these mice, we studied the ion channels and mechanisms controlling corticotroph excitability. Corticotrophs were either quiescent or electrically active, with a 22-mV difference in the resting membrane potential (RMP) between the 2 groups. In quiescent cells, CRH depolarized the membrane, leading to initial single spiking and sustained bursting; in active cells, CRH further facilitated or inhibited electrical activity and calcium spiking, depending on the initial activity pattern and CRH concentration. The stimulatory but not inhibitory action of CRH on electrical activity was mimicked by cAMP independently of the presence or absence of arachidonic acid. Removal of bath sodium silenced spiking and hyperpolarized the majority of cells; in contrast, the removal of bath calcium did not affect RMP but reduced CRH-induced depolarization, which abolished bursting electrical activity and decreased the spiking frequency but not the amplitude of single spikes. Corticotrophs with inhibited voltage-gated sodium channels fired calcium-de...Continue Reading

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Citations

Mar 23, 2017·Endocrinology·Nicola RomanòMichael J Shipston
Jun 28, 2017·Molecular and Cellular Endocrinology·Patrick A FletcherStanko S Stojilkovic
Aug 23, 2019·PLoS Computational Biology·Geir HalnesKjetil Hodne
Nov 17, 2020·Thyroid : Official Journal of the American Thyroid Association·Rafael Maso PrévideStanko S Stojilkovic
Jan 16, 2021·The Journal of Physiology·Alexandre MilmanNathalie C Guérineau
Apr 2, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hathaichanok ImphengArnaud Monteil
Jul 8, 2017·Molecular and Cellular Endocrinology·Hana Zemková, Stanko S Stojilkovic

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