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Large conductance Ca²⁺-activated K⁺ (BK) channels promote secretagogue-induced transition from spiking to bursting in murine anterior pituitary corticotrophs.

Duncan PJ, Şengül S, Tabak J, Ruth P, Bertram R, Shipston MJ - J. Physiol. (Lond.) (2015)

Bottom Line: Anterior pituitary corticotroph cells are a central component of the hypothalamic-pituitary-adrenal (HPA) axis essential for the neuroendocrine response to stress.We reveal that BK channels do not play a significant role in the generation of spontaneous activity but are critical for the transition to bursting in response to CRH.In contrast, AVP promotes an increase in single spike frequency, a mechanism independent of BK channels but dependent on background non-selective conductances.

View Article: PubMed Central - PubMed

Affiliation: Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, EH8 9XD, UK.

No MeSH data available.


Related in: MedlinePlus

CRH and AVP differentially regulate corticotroph excitabilityRepresentative traces of corticotroph cells before (A) and following (B) 0.2 nm CRH alone or before (C) and after (D) exposure to 2 nm AVP for 3 min. Summary bar graphs reveal that individually CRH and AVP can both induce an increase in event frequency (E) but only CRH is able to produce an increase in event duration which corresponds to a transition to bursting behaviour (F). Data are means ± SEM (n > 3 per group). *P < 0.05 with ANOVA in E, and Mann–Whitney U test in F, compared to base values.
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fig04: CRH and AVP differentially regulate corticotroph excitabilityRepresentative traces of corticotroph cells before (A) and following (B) 0.2 nm CRH alone or before (C) and after (D) exposure to 2 nm AVP for 3 min. Summary bar graphs reveal that individually CRH and AVP can both induce an increase in event frequency (E) but only CRH is able to produce an increase in event duration which corresponds to a transition to bursting behaviour (F). Data are means ± SEM (n > 3 per group). *P < 0.05 with ANOVA in E, and Mann–Whitney U test in F, compared to base values.

Mentions: Individually, both CRH (Fig.4A and B) and AVP (Fig.4C and D) were still able to produce an increase in corticotroph excitability. However, the patterns of stimulated excitability were distinct. Treatment of corticotrophs with 0.2 nm CRH resulted in a significant (P = 0.0057) depolarisation from –53.0 ± 2.4 mV to –43.0 ± 3.8 mV. Firing frequency increased significantly (P = 0.043) from 0.13 ± 0.07 Hz to 1.45 ± 0.68 Hz (Fig.4E). Following 10 min washout, event frequency had significantly declined to 0.40 ± 0.22 Hz in contrast to the sustained elevation of excitability observed in cells treated with combined CRH/AVP (0.88 ± 0.24 Hz). A transition from spiking to bursting was observed in all tested cells and mean event duration increased significantly (P = 0.021) from 63 ± 49 ms to 378 ± 267 ms following CRH stimulation (Fig.4F). In contrast, cells treated with 2 nm AVP alone failed to produce a significant depolarisation, but there was a significant (P = 0.033) increase in firing frequency from 0.32 ± 0.17 Hz to 1.77 ± 0.42 Hz (Fig.4E). Firing frequency remained elevated (1.33 ± 0.60 Hz) following 10 min washout suggesting that AVP promotes a sustained increase in activity. Interestingly, AVP alone failed to induce a transition from spiking to bursting in any cell examined. Mean event duration was 55 ± 46 ms under basal conditions and did not significantly increase (105 ± 78 ms) following AVP exposure (Fig.4F). AVP has been reported to stimulate intracellular Ca2+ release, although most reports utilise supraphysiological AVP levels an order of magnitude greater than used here, which are reported to activate Ca2+-activated potassium currents that produce brief hyperpolarisation in rat corticotrophs (Corcuff et al. 1993). We never see an AVP-induced hyperpolarisation under our recording conditions suggesting that either AVP (2 nm) does not significantly promote intracellular Ca2+ release in our system or this calcium elevation is not efficiently coupled to activation of Ca2+-activated potassium channels.


Large conductance Ca²⁺-activated K⁺ (BK) channels promote secretagogue-induced transition from spiking to bursting in murine anterior pituitary corticotrophs.

Duncan PJ, Şengül S, Tabak J, Ruth P, Bertram R, Shipston MJ - J. Physiol. (Lond.) (2015)

CRH and AVP differentially regulate corticotroph excitabilityRepresentative traces of corticotroph cells before (A) and following (B) 0.2 nm CRH alone or before (C) and after (D) exposure to 2 nm AVP for 3 min. Summary bar graphs reveal that individually CRH and AVP can both induce an increase in event frequency (E) but only CRH is able to produce an increase in event duration which corresponds to a transition to bursting behaviour (F). Data are means ± SEM (n > 3 per group). *P < 0.05 with ANOVA in E, and Mann–Whitney U test in F, compared to base values.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4358680&req=5

fig04: CRH and AVP differentially regulate corticotroph excitabilityRepresentative traces of corticotroph cells before (A) and following (B) 0.2 nm CRH alone or before (C) and after (D) exposure to 2 nm AVP for 3 min. Summary bar graphs reveal that individually CRH and AVP can both induce an increase in event frequency (E) but only CRH is able to produce an increase in event duration which corresponds to a transition to bursting behaviour (F). Data are means ± SEM (n > 3 per group). *P < 0.05 with ANOVA in E, and Mann–Whitney U test in F, compared to base values.
Mentions: Individually, both CRH (Fig.4A and B) and AVP (Fig.4C and D) were still able to produce an increase in corticotroph excitability. However, the patterns of stimulated excitability were distinct. Treatment of corticotrophs with 0.2 nm CRH resulted in a significant (P = 0.0057) depolarisation from –53.0 ± 2.4 mV to –43.0 ± 3.8 mV. Firing frequency increased significantly (P = 0.043) from 0.13 ± 0.07 Hz to 1.45 ± 0.68 Hz (Fig.4E). Following 10 min washout, event frequency had significantly declined to 0.40 ± 0.22 Hz in contrast to the sustained elevation of excitability observed in cells treated with combined CRH/AVP (0.88 ± 0.24 Hz). A transition from spiking to bursting was observed in all tested cells and mean event duration increased significantly (P = 0.021) from 63 ± 49 ms to 378 ± 267 ms following CRH stimulation (Fig.4F). In contrast, cells treated with 2 nm AVP alone failed to produce a significant depolarisation, but there was a significant (P = 0.033) increase in firing frequency from 0.32 ± 0.17 Hz to 1.77 ± 0.42 Hz (Fig.4E). Firing frequency remained elevated (1.33 ± 0.60 Hz) following 10 min washout suggesting that AVP promotes a sustained increase in activity. Interestingly, AVP alone failed to induce a transition from spiking to bursting in any cell examined. Mean event duration was 55 ± 46 ms under basal conditions and did not significantly increase (105 ± 78 ms) following AVP exposure (Fig.4F). AVP has been reported to stimulate intracellular Ca2+ release, although most reports utilise supraphysiological AVP levels an order of magnitude greater than used here, which are reported to activate Ca2+-activated potassium currents that produce brief hyperpolarisation in rat corticotrophs (Corcuff et al. 1993). We never see an AVP-induced hyperpolarisation under our recording conditions suggesting that either AVP (2 nm) does not significantly promote intracellular Ca2+ release in our system or this calcium elevation is not efficiently coupled to activation of Ca2+-activated potassium channels.

Bottom Line: Anterior pituitary corticotroph cells are a central component of the hypothalamic-pituitary-adrenal (HPA) axis essential for the neuroendocrine response to stress.We reveal that BK channels do not play a significant role in the generation of spontaneous activity but are critical for the transition to bursting in response to CRH.In contrast, AVP promotes an increase in single spike frequency, a mechanism independent of BK channels but dependent on background non-selective conductances.

View Article: PubMed Central - PubMed

Affiliation: Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, EH8 9XD, UK.

No MeSH data available.


Related in: MedlinePlus