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

Stimulation of corticotrophs with CRH/AVPA, representative current‐clamp recording of a corticotroph cell exposed to 0.2 nm CRH and 2 nm AVP for 3 min. Under basal conditions corticotroph cells display predominantly single‐spike action potentials (B) which transition to complex bursting patterns following CRH/AVP exposure (C). Grey shading indicates membrane potential between −50 mV and +10 mV. Summary bar graphs illustrating that stimulation with CRH/AVP results in a membrane depolarisation (D) coupled with an increase in event frequency (E), event duration (F) and burstiness factor (BF; G). Data are means ± SEM, (n = 7 per group). *P < 0.05, **P < 0.01, ***P < 0.001, Student's t test compared to base values.
© Copyright Policy - creativeCommonsBy
Related In: Results  -  Collection

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

tjp6513-fig-0002: Stimulation of corticotrophs with CRH/AVPA, representative current‐clamp recording of a corticotroph cell exposed to 0.2 nm CRH and 2 nm AVP for 3 min. Under basal conditions corticotroph cells display predominantly single‐spike action potentials (B) which transition to complex bursting patterns following CRH/AVP exposure (C). Grey shading indicates membrane potential between −50 mV and +10 mV. Summary bar graphs illustrating that stimulation with CRH/AVP results in a membrane depolarisation (D) coupled with an increase in event frequency (E), event duration (F) and burstiness factor (BF; G). Data are means ± SEM, (n = 7 per group). *P < 0.05, **P < 0.01, ***P < 0.001, Student's t test compared to base values.

Mentions: In corticotrophs isolated from POMC‐GFP male mice spontaneous activity was observed in more than 90% of cells recorded under current clamp using the perforated patch‐clamp approach, as previously observed in female corticotrophs (Liang et al. 2011) with predominantly large amplitude single‐spike action potentials (Fig. 2A and B). Very occasional longer duration bursts of activity were observed, together with single spike action potentials, in less than 6% of all corticotrophs analysed under basal conditions. Corticotrophs had a resting membrane potential of −53.7 ± 1.5 mV, displayed spontaneous action potentials at a frequency of 0.34 ± 0.14 Hz and had a mean cell capacitance of 4.43 ± 0.94 pF (Fig. 2D and E). The mean event duration of 69 ± 26 ms and a burstiness factor (BF) of 0.18 ± 0.10 are both consistent with predominantly single‐spike action potential behaviour (Fig. 2F and G) in the unstimulated state. Replacement of external sodium ions with the large organic cation N‐methyl‐d‐glucamine (NMDG+) resulted in a significant (P = 0.00059) hyperpolarisation of 22.7 ± 2.8 mV (n = 5) within 1 min, accompanied by a cessation of spontaneous activity which was fully reversible following washout. These data are consistent with those previously observed in female mouse corticotrophs and that a background sodium conductance is important for setting the resting membrane potential of corticotrophs, as in other pituitary cells (Liang et al. 2011; Tomic et al. 2011).


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)

Stimulation of corticotrophs with CRH/AVPA, representative current‐clamp recording of a corticotroph cell exposed to 0.2 nm CRH and 2 nm AVP for 3 min. Under basal conditions corticotroph cells display predominantly single‐spike action potentials (B) which transition to complex bursting patterns following CRH/AVP exposure (C). Grey shading indicates membrane potential between −50 mV and +10 mV. Summary bar graphs illustrating that stimulation with CRH/AVP results in a membrane depolarisation (D) coupled with an increase in event frequency (E), event duration (F) and burstiness factor (BF; G). Data are means ± SEM, (n = 7 per group). *P < 0.05, **P < 0.01, ***P < 0.001, Student's t test compared to base values.
© Copyright Policy - creativeCommonsBy
Related In: Results  -  Collection

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

tjp6513-fig-0002: Stimulation of corticotrophs with CRH/AVPA, representative current‐clamp recording of a corticotroph cell exposed to 0.2 nm CRH and 2 nm AVP for 3 min. Under basal conditions corticotroph cells display predominantly single‐spike action potentials (B) which transition to complex bursting patterns following CRH/AVP exposure (C). Grey shading indicates membrane potential between −50 mV and +10 mV. Summary bar graphs illustrating that stimulation with CRH/AVP results in a membrane depolarisation (D) coupled with an increase in event frequency (E), event duration (F) and burstiness factor (BF; G). Data are means ± SEM, (n = 7 per group). *P < 0.05, **P < 0.01, ***P < 0.001, Student's t test compared to base values.
Mentions: In corticotrophs isolated from POMC‐GFP male mice spontaneous activity was observed in more than 90% of cells recorded under current clamp using the perforated patch‐clamp approach, as previously observed in female corticotrophs (Liang et al. 2011) with predominantly large amplitude single‐spike action potentials (Fig. 2A and B). Very occasional longer duration bursts of activity were observed, together with single spike action potentials, in less than 6% of all corticotrophs analysed under basal conditions. Corticotrophs had a resting membrane potential of −53.7 ± 1.5 mV, displayed spontaneous action potentials at a frequency of 0.34 ± 0.14 Hz and had a mean cell capacitance of 4.43 ± 0.94 pF (Fig. 2D and E). The mean event duration of 69 ± 26 ms and a burstiness factor (BF) of 0.18 ± 0.10 are both consistent with predominantly single‐spike action potential behaviour (Fig. 2F and G) in the unstimulated state. Replacement of external sodium ions with the large organic cation N‐methyl‐d‐glucamine (NMDG+) resulted in a significant (P = 0.00059) hyperpolarisation of 22.7 ± 2.8 mV (n = 5) within 1 min, accompanied by a cessation of spontaneous activity which was fully reversible following washout. These data are consistent with those previously observed in female mouse corticotrophs and that a background sodium conductance is important for setting the resting membrane potential of corticotrophs, as in other pituitary cells (Liang et al. 2011; Tomic et al. 2011).

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