2016
DOI: 10.1210/en.2015-1899
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Spontaneous and CRH-Induced Excitability and Calcium Signaling in Mice Corticotrophs Involves Sodium, Calcium, and Cation-Conducting Channels

Abstract: Transgenic mice expressing the tdimer2(12) form of Discosoma red fluorescent protein under control of the proopiomelanocortin gene's regulatory elements are a useful model for studying corticotrophs. Using these mice, we studied the ion channels and mechanisms controlling corticotroph excitability. Corticotrophs were either quiescent or electrically active, with a 22-mV difference in the resting membrane potential (RMP) between the 2 groups. In quiescent cells, CRH depolarized the membrane, leading to initial … Show more

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Cited by 24 publications
(54 citation statements)
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“…Activated GPCRs signal through different pathways, including intracellular calcium ([Ca 2+ ] i ) signaling driven by electrical activity. Electrical excitability and associated Ca 2+ transients have been demonstrated in all endocrine pituitary cell types in vitro (Kwiecien and Hammond, 1998; Trouslard et al, 1989; Tsaneva-Atanasova et al, 2007; Chen et al, 1987; Douglas and Shibuya, 1993; Kidokoro, 1975; Kuryshev et al, 1997; Liang et al, 2011; Mollard and Schlegel, 1996; Ozawa and Sand, 1978; Tomic et al, 2015; Van Goor et al, 2001; Zemkova et al, 2016) and have also been confirmed in pituitary slices and in situ recordings (Bonnefont and Mollard, 2003; Guerineau et al, 1998).…”
Section: Introductionmentioning
confidence: 74%
See 1 more Smart Citation
“…Activated GPCRs signal through different pathways, including intracellular calcium ([Ca 2+ ] i ) signaling driven by electrical activity. Electrical excitability and associated Ca 2+ transients have been demonstrated in all endocrine pituitary cell types in vitro (Kwiecien and Hammond, 1998; Trouslard et al, 1989; Tsaneva-Atanasova et al, 2007; Chen et al, 1987; Douglas and Shibuya, 1993; Kidokoro, 1975; Kuryshev et al, 1997; Liang et al, 2011; Mollard and Schlegel, 1996; Ozawa and Sand, 1978; Tomic et al, 2015; Van Goor et al, 2001; Zemkova et al, 2016) and have also been confirmed in pituitary slices and in situ recordings (Bonnefont and Mollard, 2003; Guerineau et al, 1998).…”
Section: Introductionmentioning
confidence: 74%
“…Spontaneous spiking and bursting behavior has been reported in frog (Valentijn et al, 1991a), rat (Stack and Surprenant, 1991), mouse (Zemkova et al, 2016), and porcine (Trouslard et al, 1989) melanotrophs. Corticotrophs typically show large amplitude spikes, but may also exhibit bursting and transitions between activity patterns (Liang et al, 2011; Zemkova et al, 2016; Fletcher et al, 2017). We suggest below that this reflects their early emergence in development (see Section 4).…”
Section: Spontaneous Excitability Of Pituitary Cellsmentioning
confidence: 99%
“…Previous studies using corticotrophs isolated from male and female mice ( 12 , 13 , 34 ) revealed a robust depolarization and increase in firing frequency accompanied by a characteristic transition from spiking to bursting after CRH/AVP stimulation in metabolically intact corticotrophs. Corticotrophs in vivo would typically be exposed to CRH and AVP after an acute stressor; however, our previous data revealed that CRH primarily promotes pseudoplateau bursting, whereas AVP increases single-spike frequency ( 13 ).…”
Section: Discussionmentioning
confidence: 96%
“…In some studies of endocrine cells, APs were exclusively mediated by I Ca , and the spontaneous membrane excitability was insensitive or nearly so to TTX [1, 2, 1316]. In other studies, APs were evoked by a combination of I Ca and I Na [4, 7, 1719]. In one of these studies, TTX was found to block single, brief action potentials, while action potentials of long duration and low amplitude persisted [18], indicating the roles and different time courses of the I Ca and I Na components.…”
Section: Introductionmentioning
confidence: 99%
“…Models based on rat data have therefore typically excluded I Na [3, 9, 2330]. As TTX-sensitive spontaneous APs have been seen in mice corticotrophs [19], I Na was included in a recent computational model of these cells [31], and in a more generic murine pituitary cell model based on the previous rat and mice models [32]. However, the role of I Na in these models was mainly in modulating the firing patterns, and it was not essential for AP firing as such [31, 32].…”
Section: Introductionmentioning
confidence: 99%