LY-294002-inhibitable PI 3-kinase and regulation of baseline rates of Na(+) transport in A6 epithelia |
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Authors: | P?unescu T G Blazer-Yost B L Vlahos C J Helman S I |
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Institution: | Department of Molecular and Integrative Physiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. |
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Abstract: | Blocker-inducednoise analysis of epithelial Na+ channels (ENaCs) was usedto investigate how inhibition of an LY-294002-sensitive phosphatidylinositol 3-kinase (PI 3-kinase) alters Na+transport in unstimulated and aldosterone-prestimulated A6 epithelia. From baseline Na+ transport rates(INa) of 4.0 ± 0.1 (unstimulated) and9.1 ± 0.9 µA/cm2 (aldosterone), 10 µM LY-294002caused, following a relatively small initial increase of transport, acompletely reversible inhibition of transport within 90 min to 33 ± 6% and 38 ± 2% of respective baseline values. Initialincreases of transport could be attributed to increases of channel openprobability (Po) within 5 min to 143 ± 17% (unstimulated) and 142 ± 10% of control (aldosterone) frombaseline Po averaging near 0.5. Inhibition oftransport was due to much slower decreases of functional channeldensities (NT) to 28 ± 4% (unstimulated)and 35 ± 3% (aldosterone) of control at 90 min. LY-294002 (50 µM) caused larger but completely reversible increases ofPo (215 ± 38% of control at 5 min) andmore rapid but only slightly larger decreases ofNT. Basolateral exposure to LY-294002 induced nodetectable effect on transport, Po or NT. We conclude that an LY-294002-sensitive PI3-kinase plays an important role in regulation of transport bymodulating NT and Po ofENaCs, but only when presented to apical surfaces of the cells. |
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