Biophysical and Pharmacological Characteristics of Native Two-Pore Domain TASK Channels in Rat Adrenal Glomerulosa Cells

Lotshaw, David P.

doi:10.1007/s00232-005-7012-x

Cited by 26 publications

(28 citation statements)

References 55 publications

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“…The presence of Task3 in zona fasciculata in males might contribute to the compensation observed in male Task1 Ϫ/Ϫ mice, which recovered normal adrenal zonation of the aldosterone synthase and normal aldosterone production after puberty (15). In agreement with previous reports (6,22) and disagreement with a very recent report (17), our experiments on primary cultured adrenocortical cells showed that the K ϩ current carried by Task3 channels is a major determinant of the resting membrane potential. Surprisingly, expression of the aldosterone synthase remained restricted to the zona glomerulosa in Task3 Ϫ/Ϫ mice of both sexes and did not mimic the ectopic fasciculata expression found in Task1 Ϫ/Ϫ mice (15).…”

Section: Electrophysiology and Ca 2؉ Signaling In Task3-expressing Glsupporting

confidence: 80%

Task3 Potassium Channel Gene Invalidation Causes Low Renin and Salt-Sensitive Arterial Hypertension

Pentón¹,

Bandulik²,

Schweda

et al. 2012

Endocrinology

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Task1 and Task3 potassium channels (Task: tandem of P domains in a weak inward rectifying K ϩ channel-related acid-sensitive K ϩ channel) are believed to control the membrane voltage of aldosterone-producing adrenal glomerulosa cells. This study aimed at understanding the role of Task3 for the control of aldosterone secretion. The adrenal phenotype of Task3 Ϫ/Ϫ mice was investigated using electrophysiology, adrenal slices, and blood pressure measurements. Primary adrenocortical cells of Task3 Ϫ/Ϫ mice were strongly depolarized compared with wild-type (Ϫ52 vs.Ϫ79 mV), and in fresh adrenal slices Ca 2ϩ signaling of Task3 Ϫ/Ϫ glomerulosa cells was abnormal.In living Task3 Ϫ/Ϫ mice, the regulation of aldosterone secretion showed specific deficits: Under low Na ϩ and high K ϩ diets, protocols known to increase aldosterone, and under standard diet, Task3 inactivation was compensated and aldosterone was normal. However, high Na ϩ and low K ϩ diets, two protocols known to lower aldosterone, failed to lower aldosterone in Task3 Ϫ/Ϫ mice. The physiological regulation of aldosterone was disturbed: aldosterone-renin ratio, an indicator of autonomous aldosterone secretion, was 3-fold elevated at standard and high Na ϩ diets. Isolated adrenal glands of H igh blood pressure is one of the major cardiovascular risk factors (1). The pathogenesis of arterial hypertension, however, is very complex and encompasses environmental, genetic, vascular, and endocrine factors. Among the latter, inappropriately high aldosterone secretion is a common cause of salt and water retention resulting in hypertension. Recently, data from human genetics (2-4) pointed to a critical role of K ϩ channel defects as a cause of hyperaldosteronism.In adrenal glomerulosa cells, depolarization is considered to be the first step of a chain of events leading to aldosterone secretion (5). Glomerulosa cells have a very high K ϩ conductance leading to a hyperpolarized membrane potential close to the K ϩ equilibrium potential.

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Section: Electrophysiology and Ca 2؉ Signaling In Task3-expressing Glsupporting

confidence: 80%

Task3 Potassium Channel Gene Invalidation Causes Low Renin and Salt-Sensitive Arterial Hypertension

Pentón¹,

Bandulik²,

Schweda

et al. 2012

Endocrinology

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“…Although macroscopic K currents recorded from rat, bovine, and human ZG cells have revealed the expression of multiple voltagedependent K conductances, the mRNA for TWIK-related acidsensitive K (TASK)-1 and TASK-3 subunits is particularly abundant (20)(21)(22)(23). TASK-1 (KCNK-3, K2P3.1) and TASK-3 (KCNK-9, K2P9.1) are two closely related family members of the KCNK family of two-pore domain/four-transmembrane (2P/ 4TMS) K channels that form background or ''leak'' K channels.…”

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confidence: 99%

TASK channel deletion in mice causes primary hyperaldosteronism

Davies¹,

Hu²,

Guagliardo³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

171

166

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When inappropriate for salt status, the mineralocorticoid aldosterone induces cardiac and renal injury. Autonomous overproduction of aldosterone from the adrenal zona glomerulosa (ZG) is also the most frequent cause of secondary hypertension. Yet, the etiology of nontumorigenic primary hyperaldosteronism caused by bilateral idiopathic hyperaldosteronism remains unknown. Here, we show that genetic deletion of TWIK-related acid-sensitive K (TASK)-1 and TASK-3 channels removes an important background K current that results in a marked depolarization of ZG cell membrane potential. Although TASK channel deletion mice (TASK −/− ) adjust urinary Na excretion and aldosterone production to match Na intake, they produce more aldosterone than control mice across the range of Na intake. Overproduction of aldosterone is not the result of enhanced activity of the renin–angiotensin system because circulating renin concentrations remain either unchanged or lower than those of control mice at each level of Na intake. In addition, TASK −/− mice fail to suppress aldosterone production in response to dietary Na loading. Autonomous aldosterone production is also demonstrated by the failure of an angiotensin type 1 receptor blocker, candesartan, to normalize aldosterone production to control levels in TASK −/− mice. Thus, TASK −/− channel knockout mice exhibit the hallmarks of primary hyperaldosteronism. Our studies establish an animal model of nontumorigenic primary hyperaldosteronism and identify TASK channels as a possible therapeutic target for primary hyperaldosteronism.

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“…These behaviors are illustrated in whole-cell patch clamp records of macroscopic K + current (I K ) from a rat adrenal glomerulosa cell (Fig. 2), a cell type in which a homogenous TASK-like channel population has been found to mediate plasma membrane I K [134]. The steady-state IV relationship can be approximated by the GHK current equation over only a limited range of membrane potentials in the presence of either physiological or elevated extracellular K + concentrations; at positive potentials I K exceeded GHK predictions and at very negative potentials I K fell below GHK predictions.…”

Section: Biophysical and Pharmacological Characteristicsmentioning

confidence: 99%

“…Voltage-dependent inhibition by extracellular Mg 2+ contributed to the deviations from GHK predictions shown in Fig. 2, particularly at negative membrane potentials [134]. Extracellular Mg 2+ appeared to act as a fast channel blocker [83], reducing open channel current without affecting mean open time or macroscopic current activation and deactivation kinetics, although effects on the local K + concentration at the mouth of the pore due to shielding of surface charges [83] has not been excluded.…”

Section: Biophysical and Pharmacological Characteristicsmentioning

confidence: 99%

Biophysical, pharmacological, and functional characteristics of cloned and native mammalian two-pore domain K+ channels

Lotshaw

2007

Cell Biochem Biophys

Self Cite

163

185

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The mammalian family of two-pore domain K+ (K2P) channel proteins are encoded by 15 KCNK genes and subdivided into six subfamilies on the basis of sequence similarities: TWIK, TREK, TASK, TALK, THIK, and TRESK. K2P channels are expressed in cells throughout the body and have been implicated in diverse cellular functions including maintenance of the resting potential and regulation of excitability, sensory transduction, ion transport, and cell volume regulation, as well as metabolic regulation and apoptosis. In recent years K2P channel isoforms have been identified as important targets of several widely employed drugs, including: general anesthetics, local anesthetics, neuroprotectants, and anti-depressants. An important goal of future studies will be to identify the basis of drug actions and channel isoform selectivity. This goal will be facilitated by characterization of native K2P channel isoforms, their pharmacological properties and tissue-specific expression patterns. To this end the present review examines the biophysical, pharmacological, and functional characteristics of cloned mammalian K2P channels and compares this information with the limited data available for native K2P channels in order to determine criteria which may be useful in identifying ionic currents mediated by native channel isoforms and investigating their pharmacological and functional characteristics.

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Biophysical and Pharmacological Characteristics of Native Two-Pore Domain TASK Channels in Rat Adrenal Glomerulosa Cells

Cited by 26 publications

References 55 publications

Task3 Potassium Channel Gene Invalidation Causes Low Renin and Salt-Sensitive Arterial Hypertension

Task3 Potassium Channel Gene Invalidation Causes Low Renin and Salt-Sensitive Arterial Hypertension

TASK channel deletion in mice causes primary hyperaldosteronism

Biophysical, pharmacological, and functional characteristics of cloned and native mammalian two-pore domain K+ channels

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