| Autor: |
Claydon, T. W., Boyett, M. R., Sivaprasadarao, A., Ishii, K., Owen, J. M., O'Beirne, H. A., Leach, R., Komukai, K., Orchard, C. H. |
| Zdroj: |
Journal of Physiology; July 2000, Vol. 526 Issue: 2 p253-264, 12p |
| Abstrakt: |
1Acidosis alters the transient outward current, ito, in the heart. We have studied the mechanism underlying the effect of acidosis on one of the K+channels, Kv1.4 (heterologously expressed in Xenopus laevisoocytes), known to underlie ito.2At pH 6.5, wild‐type Kv1.4 current was inhibited during repetitive pulsing, in part as a result of a slowing of recovery from N‐type inactivation.3Acidosis still caused slowing of recovery after deletion of just one (either the first or second) of the N‐terminal inactivation ball domains. However, deletion of both the N‐terminal inactivation ball domains greatly reduced the inhibition.4As well as the N‐terminus, other parts of the channel are also required for the effect of acidosis, because, whereas the transfer of the N‐terminus of Kv1.4 to Kv1.2 conferred N‐type inactivation, it did not confer acidosis sensitivity.5Replacement of an extracellular histidine with a glutamine residue (H508Q) abolished the slowing of recovery by acidosis. Reduction of C‐type inactivation by raising the bathing K+concentration or by the mutation K532Y also abolished the slowing.6It is concluded that binding of protons to H508 enhances C‐type inactivation and this causes a slowing of recovery from N‐type inactivation and, thus, an inhibition of current during repetitive pulsing. |
| Databáze: |
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