Author's email address L. Conforti: email@example.com
Selective inhibition of a slow-inactivating voltage-dependent K+ channel in rat PC 12 cells by hypoxia
Article first published online: 30 SEP 2004
The Journal of Physiology
Volume 502, Issue 2, pages 293–305, July 1997
How to Cite
Conforti, L. and Millhorn, D. E. (1997), Selective inhibition of a slow-inactivating voltage-dependent K+ channel in rat PC 12 cells by hypoxia. The Journal of Physiology, 502: 293–305. doi: 10.1111/j.1469-7793.1997.293bk.x
- Issue published online: 30 SEP 2004
- Article first published online: 30 SEP 2004
- Received 13 January 1997; accepted 17 April 1997.
- 1Electrophysiological (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.
- 2Four 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.
- 3The 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 × open probability). Hypoxia had no effect on the 20 pS transient K+ channels, whereas reduced O2 stimulated the KCa channels.
- 4The genes encoding the α-subunits of slow-inactivating K+ channels for two members of the Shaker subfamily of K+ channels (Kvl.2 and Kvl.3) together with the Kv2.1, Kv3.1 and Kv3.2 channel genes were identified in PC12 cells.
- 5The 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 resuponsive 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).
- 6These 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.