Large- and small-conductance Ca2+-activated K+ channels: their role in the nicotinic receptor-mediated catecholamine secretion in bovine adrenal medulla

Wada, Akihiko; Urabe, Masanobu; Yuhi, Tomoaki; Yamamoto, Ryōichi; Yanagita, Toshihiko; Niina, Hiromi; Kobayashi, Hideyuki

doi:10.1007/bf00169389

Cited by 8 publications

(1 citation statement)

References 36 publications

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“…As we report here for gonadotrophs, one outcome of the presumptive increase in excitability when SK channel activity is reduced by apamin is marked enhancement in GnRH-stimulated LH secretion. Similar outcomes have been reported for adrenal chromaffin cells; apamin inhibition of SK channels augments catecholamine secretion stimulated by muscarinic or nicotinic agonists or pituitary adenylate cyclase-activating polypeptide (33)(34)(35). To our knowledge the present study is the first to demonstrate the consequences of SK channel interference for LH secretion.…”

Section: Sk Channel Functionsupporting

confidence: 88%

Ca2+-Activated K+ Channels in Gonadotropin-Releasing Hormone-Stimulated Mouse Gonadotrophs

Waring

Turgeon

2008

Endocrinology

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GnRH receptor activation elicits release of intracellular Ca(2+), which leads to secretion and also activates Ca(2+)-activated ion channels underlying membrane voltage changes. The predominant Ca(2+)-activated ion channels in rat and mouse gonadotrophs are Ca(2+)-activated K(+) channels. To establish the temporal relationship between GnRH-induced changes in intracellular [Ca(2+)] ([Ca(2+)](i)) and membrane current (I(m)), and to identify specific Ca(2+)-activated K(+) channels linking GnRH-induced increase in [Ca(2+)](i) to changes in plasma membrane electrical activity, we used single female mouse gonadotrophs in the perforated patch configuration of the patch-clamp technique, which preserves signaling pathways. Simultaneous measurement of [Ca(2+)](i) and I(m) in voltage-clamped gonadotrophs revealed that GnRH stimulates an increase in [Ca(2+)](i) that precedes outward I(m), and that activates two kinetically distinct currents identified, using specific toxin inhibitors, as small conductance Ca(2+)-activated K(+) (SK) current (I(SK)) and large (big) conductance voltage- and Ca(2+)-activated K(+) (BK) current (I(BK)). We show that the apamin-sensitive current has an IC(50) of 69 pM, consistent with the SK2 channel subtype and confirmed by immunocytochemistry. The magnitude of the SK current response to GnRH was attenuated by 17beta-estradiol (E(2)) pretreatment. Iberiotoxin, an inhibitor of BK channels, completely blocked the residual apamin-insensitive outward I(m), substantiating that I(BK) is a component of the GnRH-induced outward I(m). In contrast to its suppression of I(SK), E(2) pretreatment augmented peak I(BK). SK or BK channel inhibition modulated GnRH-stimulated LH secretion, implicating a role for these channels in gonadotroph function. In summary, in mouse gonadotrophs the GnRH-stimulated increase in [Ca(2+)](i) activates I(SK) and I(BK), which are differentially regulated by E(2) and which may be targets for E(2) positive feedback in LH secretion.

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Section: Sk Channel Functionsupporting

confidence: 88%