The sodium-activated potassium channel Slack is modulated by hypercapnia and acidosis.
Slack (Slo 2.2), a member of the Slo potassium channel family, is activated by both voltage and cytosolic factors, such as Na(+) ([Na(+)](i)) and Cl(-) ([Cl(-)](i)). Since the Slo family is known to play a role in hypoxia, and since hypoxia/ischemia is associated with an increase in H(+) and CO(2) intracellularly, we hypothesized that the Slack channel may be affected by changes in intracellular concentrations of CO(2) and H(+). To examine this, we expressed the Slack channel in Xenopus oocytes and the Slo 2.2 protein was allowed to be inserted into the plasma membrane. Inside-out patch recordings were performed to examine the response of Slack to different CO(2) concentrations (0.038%, 5%, 12%) and to different pH levels (6.3, 6.8, 7.3, 7.8, 8.3). In the presence of low [Na(+)](i) (5 mM), the Slack channel open probability decreased when exposed to decreased pH or increased CO(2) in a dose-dependent fashion (from 0.28+/-0.03, n=3, at pH 7.3 to 0.006+/-0.005, n=3, P=0.0004, at pH 6.8; and from 0.65+/-0.17, n=3, at 0.038% CO(2) to 0.22+/-0.07, n=3, P=0.04 at 12% CO(2)). In the presence of high [Na(+)](i) (45 mM), Slack open probability increased (from 0.03+/-0.01 at 5 mM [Na(+)](i), n=3, to 0.11+/-0.01, n=3, P=0.01) even in the presence of decreased pH (6.3). Since Slack activity increases significantly when exposed to increased [Na(+)](i), even in presence of increased H(+), we propose that Slack may play an important role in pathological conditions during which there is an increase in the intracellular concentrations of both acid and Na(+), such as in ischemia/hypoxia.
Ruffin
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Department of Physiology and Biophysics, Howard University College of Medicine, Washington, DC 20059, USA.
Gu
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Zhou
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Douglas
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Sun
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Trouth
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Haddad
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D000138:Acidosis / Q000378:metabolism*; D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D004594:Electrophysiology; D006863:Hydrogen-Ion Concentration; D006935:Hypercapnia / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009865:Oocytes / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010957:Plasmids / Q000235:genetics; D015221:Potassium Channels / Q000502:physiology*; D000081033:Potassium Channels, Sodium-Activated; D018075:RNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D014982:Xenopus laevis
D002712:Chlorides; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D000081033:Potassium Channels, Sodium-Activated; D018075:RNA, Complementary; C000626167:kcnt1 protein, rat; D002245:Carbon Dioxide