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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

Mathematical model of corticotroph cellsA, schematic diagram of the ionic currents in the pituitary corticotroph model. CaDOM is the free Ca2+ concentration in a microdomain and c is the mean free cytosolic Ca2+ concentration. Steady-state activation functions for the K+ (black), L-type Ca2+ (green) and K-ir (magenta) channels (B) and for the BK-far (red) and BK-near (blue) channels (C).
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fig01: Mathematical model of corticotroph cellsA, schematic diagram of the ionic currents in the pituitary corticotroph model. CaDOM is the free Ca2+ concentration in a microdomain and c is the mean free cytosolic Ca2+ concentration. Steady-state activation functions for the K+ (black), L-type Ca2+ (green) and K-ir (magenta) channels (B) and for the BK-far (red) and BK-near (blue) channels (C).

Mentions: where Cm is the membrane capacitance. There are six ionic currents in the model as shown in Fig.1A. ICa is the high voltage-activated dihydropyridine-sensitive L-type Ca2+ current that is responsible for most Ca2+ entry during an action potential. IK-dr is the rapidly activated delayed rectifier K+ current that is largely responsible for the downstroke of an action potential. The model also contains large-conductance, voltage- and Ca2+-activated K+ channels (BK channels). Some are located near Ca2+ channels and respond to Ca2+ in microdomains at open Ca2+ channels, producing the current IBK-near. Others are situated away from Ca2+ channels and respond to the mean cytosolic Ca2+ concentration, producing the current IBK-far. BK-near channels represent stress-regulated exon (STREX)-type channels, while BK-far channels represent BK channels lacking STREX insert (ZERO)-type channels (Shipston et al. 1999; Chen et al. 2005; Zhou et al. 2012) although the spatial distribution of these channel variants, or any of the channels involved in excitability in corticotrophs, is not known. IK-ir is the barium-insensitive inward rectifier K+ current that activates under hyperpolarisation. Also, the model has a current produced by non-selective-cation channels, INS. The effect of system noise is included in the model through the current Inoise.


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)

Mathematical model of corticotroph cellsA, schematic diagram of the ionic currents in the pituitary corticotroph model. CaDOM is the free Ca2+ concentration in a microdomain and c is the mean free cytosolic Ca2+ concentration. Steady-state activation functions for the K+ (black), L-type Ca2+ (green) and K-ir (magenta) channels (B) and for the BK-far (red) and BK-near (blue) channels (C).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig01: Mathematical model of corticotroph cellsA, schematic diagram of the ionic currents in the pituitary corticotroph model. CaDOM is the free Ca2+ concentration in a microdomain and c is the mean free cytosolic Ca2+ concentration. Steady-state activation functions for the K+ (black), L-type Ca2+ (green) and K-ir (magenta) channels (B) and for the BK-far (red) and BK-near (blue) channels (C).
Mentions: where Cm is the membrane capacitance. There are six ionic currents in the model as shown in Fig.1A. ICa is the high voltage-activated dihydropyridine-sensitive L-type Ca2+ current that is responsible for most Ca2+ entry during an action potential. IK-dr is the rapidly activated delayed rectifier K+ current that is largely responsible for the downstroke of an action potential. The model also contains large-conductance, voltage- and Ca2+-activated K+ channels (BK channels). Some are located near Ca2+ channels and respond to Ca2+ in microdomains at open Ca2+ channels, producing the current IBK-near. Others are situated away from Ca2+ channels and respond to the mean cytosolic Ca2+ concentration, producing the current IBK-far. BK-near channels represent stress-regulated exon (STREX)-type channels, while BK-far channels represent BK channels lacking STREX insert (ZERO)-type channels (Shipston et al. 1999; Chen et al. 2005; Zhou et al. 2012) although the spatial distribution of these channel variants, or any of the channels involved in excitability in corticotrophs, is not known. IK-ir is the barium-insensitive inward rectifier K+ current that activates under hyperpolarisation. Also, the model has a current produced by non-selective-cation channels, INS. The effect of system noise is included in the model through the current Inoise.

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