Limits...
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

Modelling the effects of CRH/AVP stimulationAdding CRH/AVP transforms spontaneous spiking to bursting in the corticotroph model. The CRH/AVP effect is modelled as an increase in gCa from 1.8 nS to 2.2 nS, an increase in gNS from 0.1 nS to 0.2 nS, a decrease in  from 20 ms to 4 ms and a decrease in  from 18 μm to 6 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4358680&req=5

fig03: Modelling the effects of CRH/AVP stimulationAdding CRH/AVP transforms spontaneous spiking to bursting in the corticotroph model. The CRH/AVP effect is modelled as an increase in gCa from 1.8 nS to 2.2 nS, an increase in gNS from 0.1 nS to 0.2 nS, a decrease in from 20 ms to 4 ms and a decrease in from 18 μm to 6 μm.

Mentions: Thus in our model we first simulated the application of CRH/AVP through changes to three ionic currents: the L-type Ca2+ current (ICa), the non-selective cation current (INS), and the BK-near current (IBK-near). Figure3A and B shows the model corticotroph cell exhibiting spontaneous spiking over the first 100 s as seen experimentally. The slow spiking is due to the noise that pushes the voltage randomly above spike threshold with the resting membrane potential set close to threshold by gNS. The application of CRH/AVP is simulated by increasing the conductances gNS and gCa (Table 1). Also, the BK-near channel time constant is decreased along with (Table 1), producing a faster activation of this current and shifting its activation curve rightward to overlap that of the BK-far activation curve (Fig.1C, blue curve becomes like red curve). After these changes to the model parameters, the low frequency spiking changes to high-frequency bursting (Fig.3A and C). Moreover, the spike amplitude decreases substantially (by ∼20 mV) and the base membrane potential increases (by ∼20 mV), as seen experimentally. The effects of drug washout is simulated by slowly changing parameters back to their original values (Fig.3A).


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)

Modelling the effects of CRH/AVP stimulationAdding CRH/AVP transforms spontaneous spiking to bursting in the corticotroph model. The CRH/AVP effect is modelled as an increase in gCa from 1.8 nS to 2.2 nS, an increase in gNS from 0.1 nS to 0.2 nS, a decrease in  from 20 ms to 4 ms and a decrease in  from 18 μm to 6 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig03: Modelling the effects of CRH/AVP stimulationAdding CRH/AVP transforms spontaneous spiking to bursting in the corticotroph model. The CRH/AVP effect is modelled as an increase in gCa from 1.8 nS to 2.2 nS, an increase in gNS from 0.1 nS to 0.2 nS, a decrease in from 20 ms to 4 ms and a decrease in from 18 μm to 6 μm.
Mentions: Thus in our model we first simulated the application of CRH/AVP through changes to three ionic currents: the L-type Ca2+ current (ICa), the non-selective cation current (INS), and the BK-near current (IBK-near). Figure3A and B shows the model corticotroph cell exhibiting spontaneous spiking over the first 100 s as seen experimentally. The slow spiking is due to the noise that pushes the voltage randomly above spike threshold with the resting membrane potential set close to threshold by gNS. The application of CRH/AVP is simulated by increasing the conductances gNS and gCa (Table 1). Also, the BK-near channel time constant is decreased along with (Table 1), producing a faster activation of this current and shifting its activation curve rightward to overlap that of the BK-far activation curve (Fig.1C, blue curve becomes like red curve). After these changes to the model parameters, the low frequency spiking changes to high-frequency bursting (Fig.3A and C). Moreover, the spike amplitude decreases substantially (by ∼20 mV) and the base membrane potential increases (by ∼20 mV), as seen experimentally. The effects of drug washout is simulated by slowly changing parameters back to their original values (Fig.3A).

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