Gonadotrophs are basophilic cells of the anterior pituitary gland specialized to secrete gonadotropins in response to elevation in intracellular calcium concentration. These cells fire action potentials (APs) spontaneously, coupled with voltage-gated calcium influx of insufficient amplitude to trigger gonadotropin release. The spontaneous excitability of gonadotrophs reflects the expression of voltage-gated sodium, calcium, potassium, non-selective cation-conducting, and chloride channels at their plasma membrane (PM). These cells also express the hyperpolarization-activated and cyclic nucleotide-gated cation channels at the PM, as well as GABAA, nicotinic, and purinergic P2X channels gated by γ-aminobutyric acid (GABA), acetylcholine (ACh), and ATP, respectively. Activation of these channels leads to initiation or amplification of the pacemaking activity, facilitation of calcium influx, and activation of the exocytic pathway. Gonadotrophs also express calcium-conducting channels at the endoplasmic reticulum membranes gated by inositol trisphosphate and intracellular calcium. These channels are activated potently by hypothalamic gonadotropin-releasing hormone (GnRH) and less potently by several paracrine calcium-mobilizing agonists, including pituitary adenylate cyclase-activating peptides, endothelins, ACh, vasopressin, and oxytocin. Activation of these channels causes oscillatory calcium release and a rapid gonadotropin release, accompanied with a shift from tonic firing of single APs to periodic bursting type of electrical activity, which accounts for a sustained calcium signaling and gonadotropin secretion. This review summarizes our current understanding of ion channels as signaling molecules in gonadotrophs, the role of GnRH and paracrine agonists in their gating, and the cross talk among channels.

• Klíčová slova
• calcium signaling, electrical activity, gonadotrophs, gonadotropin-releasing hormone, ligand-gated channels, luteinizing hormone secretion, voltage-gated channels,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

All secretory anterior pituitary cells fire action potentials spontaneously and exhibit a high resting cation conductance, but the channels involved in the background permeability have not been identified. In cultured lactotrophs and immortalized GH(3) cells, replacement of extracellular Na(+) with large organic cations, but not blockade of voltage-gated Na(+) influx, led to an instantaneous hyperpolarization of cell membranes that was associated with a cessation of spontaneous firing. When cells were clamped at -50 mV, which was close to the resting membrane potential in these cells, replacement of bath Na(+) with organic cations resulted in an outward-like current, reflecting an inhibition of the inward holding membrane current and indicating loss of a background-depolarizing conductance. Quantitative RT-PCR analysis revealed the high expression of mRNA transcripts for TRPC1 and much lower expression of TRPC6 in both lactotrophs and GH(3) cells. Very low expression of TRPC3, TRPC4, and TRPC5 mRNA transcripts were also present in pituitary but not GH(3) cells. 2-APB and SKF-96365, relatively selective blockers of TRPC channels, inhibited electrical activity, Ca(2+) influx and prolactin release in a concentration-dependent manner. Gd(3+), a common Ca(2+) channel blocker, and flufenamic acid, an inhibitor of non-selective cation channels, also inhibited electrical activity, Ca(2+) influx and prolactin release. These results indicate that nonselective cation channels, presumably belonging to the TRPC family, contribute to the background depolarizing conductance and firing of action potentials with consequent contribution to Ca(2+) influx and hormone release in lactotrophs and GH(3) cells.

• MeSH
• akční potenciály MeSH
• časové faktory MeSH
• iontové kanály účinky léků   genetika   metabolismus   MeSH
• kationtové kanály TRPC účinky léků   genetika   metabolismus   MeSH
• krysa rodu Rattus MeSH
• kultivované buňky MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• laktotropní buňky účinky léků   metabolismus   MeSH
• messenger RNA metabolismus   MeSH
• metoda terčíkového zámku MeSH
• modulátory membránového transportu farmakologie   MeSH
• polymerázová řetězová reakce s reverzní transkripcí MeSH
• potkani Sprague-Dawley MeSH
• prolaktin metabolismus   MeSH
• sodík metabolismus   MeSH
• vápník metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH
• Názvy látek
• iontové kanály MeSH
• kationtové kanály TRPC MeSH
• messenger RNA MeSH
• modulátory membránového transportu MeSH
• nonselective cation channel protein, rat MeSH Prohlížeč
• prolaktin MeSH
• sodík MeSH
• vápník MeSH

Perforated patch clamp recording was used to study the control of membrane potential (V(m)) and spontaneous electrical activity in the rat pinealocyte by norepinephrine. Norepinephrine did not alter spiking frequency. However, it was found to act through α(1B)-adrenoreceptors in a concentration-dependent manner (0.1-10 μM) to produce a biphasic change in V(m). The initial response was a hyperpolarization (∼13 mV from a resting potential of -46 mV) due to a transient (∼5 sec) outward K(+) current (∼50 pA). This current appears to be triggered by Ca(2+) released from intracellular stores, based on the observation that it was also seen in cells bathed in Ca(2+)-deficient medium. In addition, pharmacological studies indicate that this current was dependent on phospholipase C (PLC) activation and was in part mediated by bicuculline methiodide and apamin-sensitive Ca(2+)-controlled K(+) channels. The initial transient hyperpolarization was followed by a sustained depolarization (∼4 mV) due to an inward current (∼10 pA). This response was dependent on PLC-dependent activation of Na(+)/Ca(2+) influx but did not involve nifedipine-sensitive voltage-gated Ca(2+) channels. Together, these results indicate for the first time that activation of α(1B)-adrenoreceptors initiates a PLC-dependent biphasic change in pinealocyte V(m) characterized by an initial transient hyperpolarization mediated by a mixture of Ca(2+)-activated K(+) channels followed by a sustained depolarization mediated by a Ca(2+)-conducting nonselective cation channel. These observations indicate that both continuous elevation of intracellular Ca(2+) and sustained depolarization at approximately -40 mV are associated with and are likely to be required for activation of the pinealocyte.

• MeSH
• alfa-1-adrenergní receptory fyziologie   MeSH
• epifýza mozková cytologie   účinky léků   fyziologie   MeSH
• fosfolipasy typu C fyziologie   MeSH
• krysa rodu Rattus MeSH
• membránové potenciály účinky léků   MeSH
• noradrenalin farmakologie   MeSH
• potkani Sprague-Dawley MeSH
• vápník metabolismus   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Intramural MeSH
• Názvy látek
• alfa-1-adrenergní receptory MeSH
• fosfolipasy typu C MeSH
• noradrenalin MeSH
• vápník MeSH