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. 1995 Dec 15;489(Pt 3):709–721. doi: 10.1113/jphysiol.1995.sp021085

C-type inactivation controls recovery in a fast inactivating cardiac K+ channel (Kv1.4) expressed in Xenopus oocytes.

R L Rasmusson 1, M J Morales 1, R C Castellino 1, Y Zhang 1, D L Campbell 1, H C Strauss 1
PMCID: PMC1156841  PMID: 8788936

Abstract

1. A fast inactivating transient K+ current (FK1) cloned from ferret ventricle and expressed in Xenopus oocytes was studied using the two-electrode voltage clamp technique. Removal of the NH2-terminal domain of FK1 (FK1 delta 2-146) removed fast inactivation consistent with previous findings in Kv1.4 channels. The NH2-terminal deletion mutation revealed a slow inactivation process, which matches the criteria for C-type inactivation described for Shaker B channels. 2. Inactivation of FK1 delta 2-146 at depolarized potentials was well described by a single exponential process with a voltage-insensitive time constant. In the range -90 to +20 mV, steady-state C-type inactivation was well described by a Boltzmann relationship that compares closely with inactivation measured in the presence of the NH2-terminus. These results suggest that C-type inactivation is coupled to activation. 3. The coupling of C-type inactivation to activation was assessed by mutation of the fourth positively charged residue (arginine 454) in the S4 voltage sensor to glutamine (R454Q). This mutation produced a hyperpolarizing shift in the inactivation relationship of both FK1 and FK1 delta 2-146 without altering the rate of inactivation of either clone. 4. The rates of recovery from inactivation are nearly identical in FK1 and FK1 delta 2-146. 5. To assess the mechanisms underlying recovery from inactivation the effects of elevated [K+]o and selective mutations in the extracellular pore and the S4 voltage sensor were compared in FK1 and FK1 delta 2-146. The similarity in recovery rates in response to these perturbations suggests that recovery from C-type inactivation governs the overall rate of recovery of inactivated channels for both FK1 and FK1 delta 2-146. 6. Analysis of the rate of recovery of FK1 channels for inactivating pulses of different durations (70-2000 ms) indicates that recovery rate is insensitive to the duration of the inactivating pulse.

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Selected References

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  1. Armstrong C. M. Interaction of tetraethylammonium ion derivatives with the potassium channels of giant axons. J Gen Physiol. 1971 Oct;58(4):413–437. doi: 10.1085/jgp.58.4.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Busch A. E., Hurst R. S., North R. A., Adelman J. P., Kavanaugh M. P. Current inactivation involves a histidine residue in the pore of the rat lymphocyte potassium channel RGK5. Biochem Biophys Res Commun. 1991 Sep 30;179(3):1384–1390. doi: 10.1016/0006-291x(91)91726-s. [DOI] [PubMed] [Google Scholar]
  3. Campbell D. L., Giles W. R., Hume J. R., Shibata E. F. Inactivation of calcium current in bull-frog atrial myocytes. J Physiol. 1988 Sep;403:287–315. doi: 10.1113/jphysiol.1988.sp017250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Choi K. L., Aldrich R. W., Yellen G. Tetraethylammonium blockade distinguishes two inactivation mechanisms in voltage-activated K+ channels. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5092–5095. doi: 10.1073/pnas.88.12.5092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. De Biasi M., Hartmann H. A., Drewe J. A., Taglialatela M., Brown A. M., Kirsch G. E. Inactivation determined by a single site in K+ pores. Pflugers Arch. 1993 Jan;422(4):354–363. doi: 10.1007/BF00374291. [DOI] [PubMed] [Google Scholar]
  6. Gómez-Lagunas F., Armstrong C. M. The relation between ion permeation and recovery from inactivation of ShakerB K+ channels. Biophys J. 1994 Nov;67(5):1806–1815. doi: 10.1016/S0006-3495(94)80662-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hoshi T., Zagotta W. N., Aldrich R. W. Biophysical and molecular mechanisms of Shaker potassium channel inactivation. Science. 1990 Oct 26;250(4980):533–538. doi: 10.1126/science.2122519. [DOI] [PubMed] [Google Scholar]
  8. Hoshi T., Zagotta W. N., Aldrich R. W. Two types of inactivation in Shaker K+ channels: effects of alterations in the carboxy-terminal region. Neuron. 1991 Oct;7(4):547–556. doi: 10.1016/0896-6273(91)90367-9. [DOI] [PubMed] [Google Scholar]
  9. Jones S. W. Ion channels. Not an open-and-shut case. Nature. 1991 Oct 17;353(6345):603–604. doi: 10.1038/353603a0. [DOI] [PubMed] [Google Scholar]
  10. Lenfant C. NHLBI funding policies. Enhancing stability, predictability, and cost control. Circulation. 1994 Jul;90(1):1–1. doi: 10.1161/01.cir.90.1.1. [DOI] [PubMed] [Google Scholar]
  11. López-Barneo J., Hoshi T., Heinemann S. H., Aldrich R. W. Effects of external cations and mutations in the pore region on C-type inactivation of Shaker potassium channels. Receptors Channels. 1993;1(1):61–71. [PubMed] [Google Scholar]
  12. Papazian D. M., Timpe L. C., Jan Y. N., Jan L. Y. Alteration of voltage-dependence of Shaker potassium channel by mutations in the S4 sequence. Nature. 1991 Jan 24;349(6307):305–310. doi: 10.1038/349305a0. [DOI] [PubMed] [Google Scholar]
  13. Ruppersberg J. P., Stocker M., Pongs O., Heinemann S. H., Frank R., Koenen M. Regulation of fast inactivation of cloned mammalian IK(A) channels by cysteine oxidation. Nature. 1991 Aug 22;352(6337):711–714. doi: 10.1038/352711a0. [DOI] [PubMed] [Google Scholar]
  14. Russell S. N., Publicover N. G., Hart P. J., Carl A., Hume J. R., Sanders K. M., Horowitz B. Block by 4-aminopyridine of a Kv1.2 delayed rectifier K+ current expressed in Xenopus oocytes. J Physiol. 1994 Dec 15;481(Pt 3):571–584. doi: 10.1113/jphysiol.1994.sp020464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Steinberg R. A., Gorman K. B. A high-yield method for site-directed mutagenesis using polymerase chain reaction and three primers. Anal Biochem. 1994 May 15;219(1):155–157. doi: 10.1006/abio.1994.1246. [DOI] [PubMed] [Google Scholar]
  16. Tseng-Crank J., Yao J. A., Berman M. F., Tseng G. N. Functional role of the NH2-terminal cytoplasmic domain of a mammalian A-type K channel. J Gen Physiol. 1993 Dec;102(6):1057–1083. doi: 10.1085/jgp.102.6.1057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Tseng G. N., Tseng-Crank J. Differential effects of elevating [K]o on three transient outward potassium channels. Dependence on channel inactivation mechanisms. Circ Res. 1992 Sep;71(3):657–672. doi: 10.1161/01.res.71.3.657. [DOI] [PubMed] [Google Scholar]
  18. Zagotta W. N., Hoshi T., Aldrich R. W. Restoration of inactivation in mutants of Shaker potassium channels by a peptide derived from ShB. Science. 1990 Oct 26;250(4980):568–571. doi: 10.1126/science.2122520. [DOI] [PubMed] [Google Scholar]
  19. Zhang J. F., Ellinor P. T., Aldrich R. W., Tsien R. W. Molecular determinants of voltage-dependent inactivation in calcium channels. Nature. 1994 Nov 3;372(6501):97–100. doi: 10.1038/372097a0. [DOI] [PubMed] [Google Scholar]

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