Growth hormone releasing factor evokes rhythmic hyperpolarizing currents in rat anterior pituitary cells.

Nussinovitch, Itzhak

doi:10.1113/jphysiol.1988.sp016920

Cited by 30 publications

(11 citation statements)

References 55 publications

(67 reference statements)

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“…The GHRH-evoked electrophysiological response recorded in the present study differs markedly from a previous description of persistent Ca2P-dependent GHRH-evoked rhythmic hyperpolarizations recorded from loose cellattached patches (Nussinovitch, 1988). The discrepancy could be explained by the ambiguity of signal polarity in this type of cell-attached recordings.…”

Section: Discussioncontrasting

confidence: 97%

“…For example, 10 min pulses of GHRH (3 nM) every 3 h each evoke a 1 h rise in GH secretion (Weiss et al 1987). Studies with intracellular and patch clamp recording techniques of the effects of GHRH application in vitro have provided contradictory results; GHRH evokes either a small and transient depolarization (Chen, Israel & Vincent, 1989a;Naumov, Herrington & Hille, 1994) that reverses around -40 mV (Chen et al 1989a), or rhythmic hyperpolarizations (0 05 Hz) that are sensitive to Ca2+ channel blockers (Nussinovitch, 1988). The aim of the present study was to analyse the mechanisms by which somatotrophs have adapted to achieve sustained periods of GH release in response to GHRH.…”

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confidence: 99%

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Growth hormone‐releasing hormone triggers pacemaker activity and persistent Ca2+ oscillations in rat somatotrophs.

Kwiecien

Tseeb

Kurchikov

et al. 1997

The Journal of Physiology

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1. The effects of brief applications of growth hormone-releasing hormone (GHRH) to male rat somatotrophs in culture were analysed with the perforated patch clamp technique to record changes in potential or with fura-2 imaging techniques to measure variations of cytosolic Ca2+ concentration ([Ca2+]1). 2. Silent somatotrophs (n = 61) had a mean resting potential of -37 + 1 mV and a mean basal [Ca2+]. of 30 + 4 nM. Brief GHRH applications (30 nM, 40 s) triggered rhythmic action potentials (23-6 + 0 9 mV, 613 + 82 ms, 0X21 + 0-02 Hz) and [Ca2+], increase (to 352 + 30 nM) followed by rhythmic [Ca2+]i transients (to 138 + 6 nM) that persisted up to 90 min after the last GHRH application. Both action potentials and [Ca2+], transients were totally and reversibly blocked by removing external Ca2P or Nae or by adding inorganic Ca2+ channel blockers or nifedipine (3 uM).3. Somatostatin (1-300 nM), carbamylcholine (0 1-1 /M) and muscarine (0 1-1 jM) each had a dose-dependent inhibitory effect, from a decrease of Ca2+ spike duration and frequency to a complete block of the GHRH-evoked action potentials. 4. The present results show that somatotrophs in culture have intrinsic membrane properties that allow them to sustain a pacemaker activity and subsequent long-lasting sequences of[Ca2+], oscillations triggered by short pulses of GHRH and inhibited by somatostatin and muscarinic agonists.Pulsatile growth hormone (GH) secretion by somatotrophs is a complex process that includes control by at least two hypothalamic factors with opposite actions, the GH-releasing hormone (GHRH) and somatostatin, the GH-releaseinhibiting hormone (see review by Bertherat, Bluet-Pajot & Epelbaum, 1995). In addition, a variety of substances, including neurotransmitters, neuropeptides, growth factors and cytokines, endogenous to the anterior pituitary gland, can act as local modulators of somatotroph activity in a paracrine or autocrine manner (Houben & Denef, 1990). In the male rat, GH release is characterized by a striking regular ultradian rhythm composed of GH peaks of 1 h duration every 3-4 h (Tannenbaum & Martin, 1976). In vitro, brief (4-10 min) GHRH applications evoke a longlasting GH secretion in perifused anterior pituitary cells (Sheppard, Moor & Kraicer, 1985;Kato & Suzuki, 1986; Weiss, Cronin & Thorner, 1987). For example, 10 min pulses of GHRH (3 nM) every 3 h each evoke a 1 h rise in GH secretion (Weiss et al. 1987). Studies with intracellular and patch clamp recording techniques of the effects of GHRH application in vitro have provided contradictory results; GHRH evokes either a small and transient depolarization (Chen, Israel & Vincent, 1989a;Naumov, Herrington & Hille, 1994) perfused at a rate of 2-5 ml min-'. The Na+-free solution was A prepared by substituting choline chloride or tris(hydroxymethyl) aminomethane (Tris) for NaCl in the standard solution. The low-Clsolution was prepared by substituting isethionic acid (sodium salt)for NaCl in the standard solution. The Ca2+-free solution was prepared by adding 1 mm EGTA to a Ca2+...

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Section: Discussioncontrasting

confidence: 97%

mentioning

confidence: 99%

Growth hormone‐releasing hormone triggers pacemaker activity and persistent Ca2+ oscillations in rat somatotrophs.

Kwiecien

Tseeb

Kurchikov

et al. 1997

The Journal of Physiology

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“…This dialysis is rapid (< 2 min) as seen by the stabilization of the baseline current after this time, and the disappearance of K+ currents when using a Cs+-filled electrode. This unresponsiveness to a releasing factor following dialysis of the cell contents has been previously reported for both TRH activation of GH3/B6 cells (Dufy, Jaken & Barker, 1987), and GHRH effects on rat anterior pituitary cells (Nussinovitch, 1988). Thus we cannot rule out the possibility that voltage-activated currents are involved in somatotroph activation by bGHRH.…”

Section: Voltage-activated Currents In Somatotrophssupporting

confidence: 78%

Whole‐cell recordings of ionic currents in bovine somatotrophs and their involvement in growth hormone secretion.

Mason

Rawlings

1988

The Journal of Physiology

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SUMMARY1. The whole-cell mode of the patch-clamp technique was used to record voltage-activated cationic currents in immunocytochemically identified bovine somatotrophs.2. In current-clamp mode, cells had a resting membrane potential of -83-0+ 4-5 mV, and an input resistance of 8-4 + 2-1 GS2. Cells rarely fired action potentials spontaneously, but fired one to three action potentials in response to a suprathreshold current pulse.3. Under voltage clamp, in Ca2+-free media, the action potential was shown to be composed of a TTX-sensitive inward Na+ current and an outward K+ current.4. The isolated Na+ current had a threshold of approximately -50 mV, and rapidly activated and then inactivated to a small steady-state current. Peak Na+ current amplitude with 140 mM-external Na+ was 341-1 + 33.5 pA (n = 14) at a membrane potential of -32-1 + 2-4 mV (n = 14).5. With Ca2+ or Ba2+ (5-30 mM) as the only membrane-permeable cation, voltage pulses to potentials more positive than -55 mV from a holding potential of -80 mV revealed a rapidly activating current component that was followed by a second, very slowly inactivating, current component, most clearly seen with Ba2+. Both components were maximally activated between 0 and +10 mV, were TTX insensitive, but were blocked by 4 mM-CO2+.6. Three components of the isolated K+ current were identified (IAs IK and IK(ca)) by their voltage sensitivity, Ca2+ dependence and their response to 4-aminopyridine (4-AP) and tetraethylammonium (TEA).7. Growth hormone (GH)-releasing hormone (GHRH) applied to cells under whole-cell voltage clamp had no effect on either steady-state or voltage-activated ionic currents. This is probably due to dialysis of cytoplasmic compounds vital for GHRH activation of the cell.8. Both basal and GHRH-stimulated GH secretion were unaffected by TTX, implying that the Na+ action potential is not critical for such release. In contrast the Ca21 channel blocker Co2+ attenuated GH release in both cases. The K+ channel blocker TEA stimulated GH release above basal and GHRH-stimulated levels.

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“…Anterior pituitary cells display cell‐type specific spontaneous and stimulated rhythmic electrical activity . This electrical activity is generated by a repertoire of voltage‐gated channels that are differently expressed in different pituitary cell types .…”

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confidence: 99%

Multiple Pathways for High Voltage‐Activated Ca²⁺ Influx in Anterior Pituitary Lactotrophs and Somatotrophs

Tzour

Sosial

Meir

et al. 2012

J Neuroendocrinology

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The present study demonstrates that a significant proportion of high voltage-activated (HVA) Ca(2+) influx in native rat anterior pituitary cells is carried through non-L-type Ca(2+) channels. Using whole-cell patch-clamp recordings and specific Ca(2+) channel toxin blockers, we show that approximately 35% of the HVA Ca(2+) influx in somatotrophs and lactotrophs is carried through Ca(v) 2.1, Ca(v) 2.2 and Ca(v) 2.3 channels, and that somatotrophs and lactotrophs share similar proportions of these non-L-type Ca(2+) channels. Furthermore, experiments on mixed populations of native anterior pituitary cells revealed that the fraction of HVA Ca(2+) influx carried through these non-L-type Ca(2+) channels might even be higher (approximately 46%), suggesting that non-L-type channels exist in the majority of native anterior pituitary cells. Using western blotting, immunoblots for α(1C) , α(1D) , α(1A) , α(1B) and α(1E) Ca(2+) channel subunits were identified in native rat anterior pituitary cells. Additionally, using reverse transcriptase-polymerase chain reaction, cDNA transcripts for α(1C) , α(1D) , α(1A) and α(1B) Ca(2+) channel subunits were identified. Transcripts for α(1E) were nonspecific and transcripts for α(1S) were not detected at all (control). Taken together, these results clearly demonstrate the existence of multiple HVA Ca(2+) channels in the membrane of rat native anterior pituitary cells. Whether these channels are segregated among different membrane compartments was investigated further in flotation assays, demonstrating that Ca(v) 2.1, Ca(v) 1.2 and caveolin-1 were mostly localised in light fractions of Nycodenz gradients (i.e. in lipid raft domains). Ca(v) 1.3 channels were distributed among both light and heavy fractions of the gradients (i.e. among raft and nonraft domains), whereas Ca(v) 2.2 and Ca(v) 2.3 channels were distributed mostly among nonraft domains. In summary, in the present study, we demonstrate multiple pathways for HVA Ca(2+) influx through L-type and non-L-type Ca(2+) channels in the membrane of native anterior pituitary cells. The compartmentalisation of these channels among raft and nonraft membrane domains might be essential for their proper regulation by separate receptors and signalling pathways.

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Growth hormone releasing factor evokes rhythmic hyperpolarizing currents in rat anterior pituitary cells.

Cited by 30 publications

References 55 publications

Growth hormone‐releasing hormone triggers pacemaker activity and persistent Ca2+ oscillations in rat somatotrophs.

Growth hormone‐releasing hormone triggers pacemaker activity and persistent Ca2+ oscillations in rat somatotrophs.

Whole‐cell recordings of ionic currents in bovine somatotrophs and their involvement in growth hormone secretion.

Multiple Pathways for High Voltage‐Activated Ca²⁺ Influx in Anterior Pituitary Lactotrophs and Somatotrophs

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Growth hormone releasing factor evokes rhythmic hyperpolarizing currents in rat anterior pituitary cells.

Cited by 30 publications

References 55 publications

Growth hormone‐releasing hormone triggers pacemaker activity and persistent Ca2+ oscillations in rat somatotrophs.

Growth hormone‐releasing hormone triggers pacemaker activity and persistent Ca2+ oscillations in rat somatotrophs.

Whole‐cell recordings of ionic currents in bovine somatotrophs and their involvement in growth hormone secretion.

Multiple Pathways for High Voltage‐Activated Ca2+ Influx in Anterior Pituitary Lactotrophs and Somatotrophs

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Multiple Pathways for High Voltage‐Activated Ca²⁺ Influx in Anterior Pituitary Lactotrophs and Somatotrophs