SK4/IK1-like channels mediate TEA-insensitive,  Ca<sup>2+</sup>-activated K<sup>+</sup> currents in bovine parotid acinar cells

Takahata, T.; Hayashi, Mikio; Ishikawa, Takahiro

doi:10.1152/ajpcell.00250.2002

Cited by 38 publications

(40 citation statements)

References 54 publications

(96 reference statements)

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“…Some SK Ca channels, e.g. SK4 and SK ap-ins (apamin-insensitive), share pharmacological characteristics with IK Ca channels [13,32,35], which might reflect the high degree of structural homology between SK4 and mIK1 [37]. However, the I/V curves of apamin-insensitive, ChTX-sensitive SK4 channels differ from those of IK Ca channels, in that the SK4 I/V are linear at potentials positive to 50 mV [13,32].…”

Section: Discussionmentioning

confidence: 99%

Characteristics and a functional implication of Ca 2+ -activated K + current in mouse aortic endothelial cells

Ahn

Seol²,

Kim³

et al. 2004

Pfl�gers Archiv European Journal of Physiology

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We employed the patch-clamp technique to investigate a Ca(2+)-activated K(+) (K(Ca)) current in cultured mouse aortic endothelial cells (MAECs). In the whole-cell mode, an increase in cytosolic [Ca(2+)] ([Ca(2+)](i)) to 2 micro M activated an outwards current. The [K(+)](o)-dependent change of the reversal potentials agreed well with the predicted Nernstian relation, suggesting that it was a K(Ca) current. The Hill coefficient (4) and EC(50) (740 nM) were obtained from the current/[Ca(2+)](i) relationship. Iberiotoxin (50 nM) or apamin (200 nM) failed to inhibit the current, whereas TEA (10 mM) suppressed the current to 73.6+/-1.6% of control ( n=9). The intermediate-conductance, Ca(2+)-activated K(+) (IK(Ca)) channel blockers charybdotoxin (50 nM), clotrimazole (10 micro M) and econazole (10 micro M) inhibited the K(Ca) current to 10.5+/-1.3% ( n=6), 16.6+/-3.1% ( n=6), and 19.3+/-2.5% ( n=5) of control, respectively. The IK(Ca) channel openers chlorzoxazone, zoxazolamine and 1-ethyl-2-benz-imidazolinone and the Ca(2+)-activated Cl(-) channel blocker niflumic acid activated the K(Ca) current. In inside-out patches, the single-channel conductance was 17.7 pS in symmetrical K(+) solutions. RT-PCR analysis showed transcripts of the murine IK1 channel (mIK1) in MAECs. The IK(Ca) channel blockers inhibited the ATP-induced [Ca(2+)](i) increase in MAECs and the endothelium-dependent relaxation of mouse aortic rings. In addition, the IK(Ca) channel openers augmented ATP-induced [Ca(2+)](i) increase in MAECs and evoked endothelium-dependent relaxation of mouse aorta. These results suggest that an mIK1-like channel mediates the native IK(Ca) current in MAECs and may contribute to endothelium-dependent relaxation by modulating MAEC [Ca(2+)](i).

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Section: Discussionmentioning

confidence: 99%

Characteristics and a functional implication of Ca 2+ -activated K + current in mouse aortic endothelial cells

Ahn

Seol²,

Kim³

et al. 2004

Pfl�gers Archiv European Journal of Physiology

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“…1). KCNN4 is expressed abundantly in epithelial cells of colon [107] and of salivary glands [75,95] and less in small intestine [34,41]. However, during cAMPmediated intestinal Cl secretion, KCNN4 activity is very low due to a reduction of intracellular Ca 2+ .…”

Section: Basolateral Epithelial K + Channels: Driving Force and Cell mentioning

confidence: 99%

Potassium channels in epithelial transport

Warth

2003

Pflugers Arch - Eur J Physiol

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“…Both exocrine and other fluid-secreting epithelia often express K ϩ channels whose activity can facilitate Cl Ϫ efflux by maintaining a hyperpolarized membrane voltage. Rodent (and other) salivary glands express two types of Ca 2ϩ -activated potassium channels, a BK channel and an IK channel (17)(18)(19)(20)(21)(22). These BK and IK channels have biophysical and pharmacological properties consistent with those expected of channels encoded by the Slo (Kcnma1) and Kcnn4 genes, respectively (6,22).…”

mentioning

confidence: 96%

“…Rodent (and other) salivary glands express two types of Ca 2ϩ -activated potassium channels, a BK channel and an IK channel (17)(18)(19)(20)(21)(22). These BK and IK channels have biophysical and pharmacological properties consistent with those expected of channels encoded by the Slo (Kcnma1) and Kcnn4 genes, respectively (6,22). Both channels are activated by the increase in intracellular Ca 2ϩ produced by muscarinic agonists, but the evidence suggests that fluid secretion may be independent of BK channel activity (17,20,23), leaving IK channels to play this role.…”

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confidence: 99%

Physiological Roles of the Intermediate Conductance, Ca2+-activated Potassium Channel Kcnn4

Begenisich

Nakamoto

Ovitt

et al. 2004

Journal of Biological Chemistry

177

182

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Three broad classes of Ca2؉ -activated potassium channels are defined by their respective single channel conductances, i.e. the small, intermediate, and large conductance channels, often termed the SK, IK, and BK channels, respectively. SK channels are likely encoded by three genes, Kcnn1-3, whereas IK and most BK channels are most likely products of the Kcnn4 and Slo (Kcnma1) genes, respectively. IK channels are prominently expressed in cells of the hematopoietic system and in organs involved in salt and fluid transport, including the colon, lung, and salivary glands. IK channels likely underlie the K ؉ permeability in red blood cells that is associated with water loss, which is a contributing factor in the pathophysiology of sickle cell disease. IK channels are also involved in the activation of T lymphocytes. The fluid-secreting acinar cells of the parotid gland express both IK and BK channels, raising questions about their particular respective roles. To test the physiological roles of channels encoded by the Kcnn4 gene, we constructed a mouse deficient in its expression. Kcnn4 null mice were of normal appearance and fertility, their parotid acinar cells expressed no IK channels, and their red blood cells lost K ؉ permeability. The volume regulation of T lymphocytes and erythrocytes was severely impaired in Kcnn4 null mice but was normal in parotid acinar cells. Despite the loss of IK channels, activated fluid secretion from parotid glands was normal. These results confirm that IK channels in red blood cells, T lymphocytes, and parotid acinar cells are indeed encoded by the Kcnn4 gene. The role of these channels in water movement and the subsequent volume changes in red blood cells and T lymphocytes is also confirmed. Surprisingly, Kcnn4 channels appear to play no required role in fluid secretion and regulatory volume decrease in the parotid gland.It has become clear that multiple types of Ca 2ϩ -activated potassium channels underlie a wide range of distinct physiological processes. Physiological and pharmacological analyses have subdivided Ca 2ϩ -activated potassium channels into three groups, i.e. the small, intermediate, and large conductance channels, often termed SK, 1 IK, and BK channels, respectively. IK channels, as their designation implies, have a single channel conductance intermediate between the SK and BK channels. These three functional groups have rather distinct pharmacological profiles, and SK, IK, and BK channels can be specifically blocked by apamin, clotrimazole, and paxilline, respectively. SK and IK channels are encoded by four genes of the KCNN gene family. The three SK channels, KCNN1-3, share ϳ70 -75% amino acid identity. The IK channel KCNN4 is encoded by a protein sharing only ϳ40% amino acid identity with each of the three SK channels, KCNN1-3.

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SK4/IK1-like channels mediate TEA-insensitive, Ca²⁺-activated K⁺ currents in bovine parotid acinar cells

Abstract: Takahata, T., M. Hayashi, and T. Ishikawa. SK4/IK1-like channels mediate TEA-insensitive, Ca 2ϩ -activated K ϩ currents in bovine parotid acinar cells.

Cited by 38 publications

References 54 publications

Characteristics and a functional implication of Ca 2+ -activated K + current in mouse aortic endothelial cells

Characteristics and a functional implication of Ca 2+ -activated K + current in mouse aortic endothelial cells

Potassium channels in epithelial transport

Physiological Roles of the Intermediate Conductance, Ca2+-activated Potassium Channel Kcnn4

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SK4/IK1-like channels mediate TEA-insensitive, Ca2+-activated K+ currents in bovine parotid acinar cells

Abstract: Takahata, T., M. Hayashi, and T. Ishikawa. SK4/IK1-like channels mediate TEA-insensitive, Ca 2ϩ -activated K ϩ currents in bovine parotid acinar cells.

Cited by 38 publications

References 54 publications

Characteristics and a functional implication of Ca 2+ -activated K + current in mouse aortic endothelial cells

Characteristics and a functional implication of Ca 2+ -activated K + current in mouse aortic endothelial cells

Potassium channels in epithelial transport

Physiological Roles of the Intermediate Conductance, Ca2+-activated Potassium Channel Kcnn4

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SK4/IK1-like channels mediate TEA-insensitive, Ca²⁺-activated K⁺ currents in bovine parotid acinar cells