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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

Simulations of CRH and AVP aloneA, basal spiking activity. B, CRH alone transforms spiking to high frequency bursting due to changes in the currents ICa (gCa is increased from 1.8 nS to 2.2 nS) and IBK-near ( is decreased from 20 ms to 4 ms and  is decreased from 18 μm to 6 μm).C, AVP alone modulates INS (gNS is increased from 0.1 nS to 0.2 nS) which leads to fast spiking.
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fig05: Simulations of CRH and AVP aloneA, basal spiking activity. B, CRH alone transforms spiking to high frequency bursting due to changes in the currents ICa (gCa is increased from 1.8 nS to 2.2 nS) and IBK-near ( is decreased from 20 ms to 4 ms and is decreased from 18 μm to 6 μm).C, AVP alone modulates INS (gNS is increased from 0.1 nS to 0.2 nS) which leads to fast spiking.

Mentions: The experimental findings we observed after the addition of CRH only or AVP only were further investigated in our model. In the experiments, adding only CRH (without AVP) changes the basal single-spike activity to bursting (Fig.4A and B). Since CRH may act on several conductances, we asked which conductances were necessary for conversion to bursting. We found that increasing either the non-selective-cation current conductance gNS or Ca2+ current conductance gCa increases spike frequency but does not produce bursting. However, making the BK-near channels similar to BK-far by reducing of the BK-near channel from 20 ms to 4 ms and right-shifting its activation curve ( from 18 to 6 μm) is sufficient to convert spiking to bursting without the need to make any other changes (Fig.5A and B). A small additional increase of the L-type conductance did not prevent that transition to bursting, but increased burst frequency and amplitude.


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)

Simulations of CRH and AVP aloneA, basal spiking activity. B, CRH alone transforms spiking to high frequency bursting due to changes in the currents ICa (gCa is increased from 1.8 nS to 2.2 nS) and IBK-near ( is decreased from 20 ms to 4 ms and  is decreased from 18 μm to 6 μm).C, AVP alone modulates INS (gNS is increased from 0.1 nS to 0.2 nS) which leads to fast spiking.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig05: Simulations of CRH and AVP aloneA, basal spiking activity. B, CRH alone transforms spiking to high frequency bursting due to changes in the currents ICa (gCa is increased from 1.8 nS to 2.2 nS) and IBK-near ( is decreased from 20 ms to 4 ms and is decreased from 18 μm to 6 μm).C, AVP alone modulates INS (gNS is increased from 0.1 nS to 0.2 nS) which leads to fast spiking.
Mentions: The experimental findings we observed after the addition of CRH only or AVP only were further investigated in our model. In the experiments, adding only CRH (without AVP) changes the basal single-spike activity to bursting (Fig.4A and B). Since CRH may act on several conductances, we asked which conductances were necessary for conversion to bursting. We found that increasing either the non-selective-cation current conductance gNS or Ca2+ current conductance gCa increases spike frequency but does not produce bursting. However, making the BK-near channels similar to BK-far by reducing of the BK-near channel from 20 ms to 4 ms and right-shifting its activation curve ( from 18 to 6 μm) is sufficient to convert spiking to bursting without the need to make any other changes (Fig.5A and B). A small additional increase of the L-type conductance did not prevent that transition to bursting, but increased burst frequency and amplitude.

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