Selective inhibition of a slow-inactivating voltage-dependent K+ channel in rat PC12 cells by hypoxia

J Physiol. 1997 Jul 15;502 ( Pt 2)(Pt 2):293-305. doi: 10.1111/j.1469-7793.1997.293bk.x.

Abstract

1. Electrophysiological (single-channel patch clamp) and molecular biological experiments (reverse transcriptase-polymerase chain reaction) were performed to attempt to identify the O2-sensitive K+ channel in rat phaeochromocytoma (PC12) cells. 2. Four types of K+ channels were recorded in PC12 cells: a small-conductance K+ channel (14 pS), a calcium-activated K+ channel (KCa; 102 pS) and two K+ channels with similar conductance (20 pS). These last two channels differed in their time-dependent inactivation: one was a slow-inactivating channel, while the other belonged to the family of fast transient K+ channels. 3. The slow-inactivating 20 pS K+ channel was inhibited by hypoxia. Exposure to hypoxia produced a 50% reduction in channel activity (number of active channels in the patch x open probability). Hypoxia had no effect on the 20 pS transient K+ channels, whereas reduced O2 stimulated the KCa channels. 4. The genes encoding the alpha-subunits of slow-inactivating K+ channels for two members of the Shaker subfamily of K+ channels (Kv1.2 and Kv1.3) together with the Kv2.1, Kv3.1 and Kv3.2 channel genes were identified in PC12 cells. 5. The expression of the Shaker Kv1.2, but none of the other K+ channel genes, increased in cells exposed to prolonged hypoxia (18 h). The same cells were more responsive to a subsequent exposure to hypoxia (35% inhibition of K+ current measured in whole-cell voltage clamp) compared with the cells maintained in normoxia (19% inhibition). 6. These results indicate that the O2-sensitive K+ channel in PC12 cells is a 20 pS slow-inactivating K+ channel that is upregulated by hypoxia. This channel appears to belong to the Shaker subfamily of voltage-gated K+ channels.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenal Gland Neoplasms
  • Animals
  • Cell Hypoxia*
  • Electric Conductivity
  • Gene Expression
  • Membrane Potentials
  • Oxygen / pharmacology
  • PC12 Cells
  • Patch-Clamp Techniques
  • Pheochromocytoma
  • Polymerase Chain Reaction
  • Potassium Channel Blockers
  • Potassium Channels / biosynthesis
  • Potassium Channels / physiology*
  • Rats

Substances

  • Potassium Channel Blockers
  • Potassium Channels
  • Oxygen