First Author | Attali B | Year | 1992 |
Journal | J Biol Chem | Volume | 267 |
Issue | 12 | Pages | 8650-7 |
PubMed ID | 1373731 | Mgi Jnum | J:931 |
Mgi Id | MGI:49463 | Doi | 10.1016/s0021-9258(18)42492-1 |
Citation | Attali B, et al. (1992) Cloning, functional expression, and regulation of two K+ channels in human T lymphocytes. J Biol Chem 267(12):8650-7 |
abstractText | Low stringency screening of a Jurkat cDNA library with a rat brain K+ channel (RCK1) probe has resulted in the isolation of HLK3, a voltage-gated K+ channel. In Xenopus oocytes, the HLK3 clone directs the expression of a rapidly activating transient outward K+ current similar to the type n K+ current recorded in Jurkat T cells. The HLK3 gene is located on the short arm of human chromosome 1 (p13.3). Polymerase chain reaction was used to clone HIsK from Jurkat cDNA. The HIsK clone shares the same sequence with a previously described genomic clone (Murai, T., Kazikuka, A., Takumi, T., Ohkubo, H., and Nakanishi, S. (1989) Biochem. Biophys. Res. Commun. 161, 176-181). In Xenopus oocytes, it encodes a slowly activating, noninactivating K+ channel which cannot be recorded in Jurkat cells by conventional patch-clamp techniques. Transcripts of both clones are present at a similar level before and after activation of purified human T lymphocytes and Jurkat cells, reflecting a constitutive expression of K+ channel messages. This finding is in good agreement with the electrophysiological results for type n K+ current density on the same cells. HLK3 current is very sensitive to the scorpion toxin charybdotoxin (IC50 = 0.8 nM). HIsK current is totally insensitive to this toxin but is blocked by the antiarrhythmic clofilium (IC50 = 80 microM). While charybdotoxin has no effect on interleukin 2 mRNA induction, clofilium potently inhibits interleukin 2 mRNA expression upon mitogen-induced T cell activation. It is concluded that the HLK3 channel is not an important component of the T cell mitogenic response. Other targets for K+ channel blockers, such as the HIsK protein, could be involved in the activation process. |