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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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tjp6513-fig-0001: 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: The Hodgkin–Huxley formalism is used (Hodgkin & Huxley, 1952) with currents that are present in pituitary corticotrophs. In our model, the potential difference across the plasma membrane varies according to:(1)CmdVdt=−(I Ca +IK‐ dr +I BK ‐ near +I BK ‐ far +IK‐ ir +I NS +I noise )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 - creativeCommonsBy
Related In: Results  -  Collection

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

tjp6513-fig-0001: 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: The Hodgkin–Huxley formalism is used (Hodgkin & Huxley, 1952) with currents that are present in pituitary corticotrophs. In our model, the potential difference across the plasma membrane varies according to:(1)CmdVdt=−(I Ca +IK‐ dr +I BK ‐ near +I BK ‐ far +IK‐ ir +I NS +I noise )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