Phosphorylation modulates the activity of the ATP-sensitive K+ channel in the ventromedial hypothalamic nucleus

V. H. Routh, J. J. McArdle, B. E. Levin

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Regulation of the ATP-sensitive K+ (K-ATP) channel was examined in cell-attached and inside-out membrane patches of freshly isolated neurons from the ventromedial hypothalamic nucleus (VMN) of 7-14 day old male Sprague-Dawley rats. When inside-out patches were exposed to symmetrical K+, the reversal potential was -2.85 ± 1.65 mV, the single channel conductance 46 pS, and the total conductance varied as a multiple of this value. Glucose (10 mM) reversibly inhibited channel activity in cell-attached preparations by 81%. In the presence of 0.1 mM ADP, 10, 5, and 1 mM ATP reversibly inhibited VMN K-ATP channels in inside-out patches by 88, 83, and 60%, respectively. This inhibition was not dependent on phosphorylation since 5 mM AMPPNP, the non-hydrolyzable analog of ATP, reversibly inhibited channel activity by 67%. Relatively high concentrations of glibenclamide (100 μM) also reversibly inhibited VMN K-ATP channel activity in cell attached and inside-out patches by 7 and 79%, respectively. Finally, the non-specific kinase inhibitor H7 (200 μM) decreased channel activity by 53% while the non-specific phosphatase inhibitor microcystin (250 mM) increased channel activity by 218%. These data suggest that while the inhibitory effect of ATP is not phosphorylation dependent, phosphorylation state is an important regulator of the VMN K-ATP channel.

Original languageEnglish (US)
Pages (from-to)107-119
Number of pages13
JournalBrain research
Volume778
Issue number1
DOIs
StatePublished - Dec 5 1997

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Keywords

  • AMPPNP
  • ATP-sensitive K channel
  • Glibenclamide
  • Glucose
  • Metabolism
  • Phosphorylation
  • Ventromedial hypothalamic nucleus

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