Mutations in the K+ channel signature sequence

Heginbotham, Lise; Lü, Zhe; Abramson, Tatiana; MacKinnon, Roderick

doi:10.1016/s0006-3495(94)80887-2

Cited by 784 publications

(654 citation statements)

References 54 publications

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“…All other identified human two-pore K ϩ channels, such as TREK-1(KCNK2), share Ͻ30% amino acid identity with SUP-9. Most of the amino acid identities among SUP-9 and the human TASK channels are restricted to the P domains, highly conserved loops that determine the ion selectivity of K ϩ channels (Heginbotham et al, 1994), and to the first, second, and fourth transmembrane domains.…”

Section: Resultsmentioning

confidence: 99%

sup-9, sup-10, andunc-93May Encode Components of a Two-Pore K⁺Channel that Coordinates Muscle Contraction inCaenorhabditis elegans

et al. 2003

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Genetic studies of sup-9, unc-93, and sup-10 strongly suggest that these genes encode components of a multi-subunit protein complex that coordinates muscle contraction in Caenorhabditis elegans. We cloned sup-9 and sup-10 and found that they encode a two-pore K ϩ channel and a novel transmembrane protein, respectively. We also found that UNC-93 and SUP-10 colocalize with SUP-9 within muscle cells, and that UNC-93 is a member of a novel multigene family that is conserved among C. elegans, Drosophila, and humans. Our results indicate that SUP-9 and perhaps other two-pore K ϩ channels function as multiprotein complexes, and that UNC-93 and SUP-10 likely define new classes of ion channel regulatory proteins.

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Section: Resultsmentioning

confidence: 99%

sup-9, sup-10, andunc-93May Encode Components of a Two-Pore K⁺Channel that Coordinates Muscle Contraction inCaenorhabditis elegans

et al. 2003

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“…K ϩ -selective channels have the amino acid triplet "GYG" motif in the selectivity filter within the ionconducting pore of the channel (Fig. 2); this has been demonstrated to be the basis for the strong discrimination against Na ϩ conduction by these channels (Heginbotham et al, 1994;Doyle et al, 1998). Analysis of the deduced amino acid sequences of cloned animal cngcs has noted that this critical GYG motif within the selectivity filter of the pore is absent, and that this is the likely basis for Na ϩ conduction by cngcs (Finn et al, 1996;Zagotta and Siegelbaum, 1996).…”

Section: Cation Selectivitymentioning

confidence: 99%

Electrophysiological Analysis of Cloned Cyclic Nucleotide-Gated Ion Channels

et al. 2002

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Electrophysiological studies were conducted on the cloned plant cyclic nucleotide-gated ion channels AtCNGC2 and AtCNGC1 from Arabidopsis, and NtCBP4 from tobacco (Nicotiana tobacum). The nucleotide coding sequences for these proteins were expressed in Xenopus laevis oocytes or HEK 293 cells. Channel characteristics were evaluated using voltage clamp analysis of currents in the presence of cAMP. AtCNGC2 was demonstrated to conduct K ϩ and other monovalent cations, but exclude Na ϩ ; this conductivity profile is unique for any ion channel not possessing the amino acid sequence found in the selectivity filter of K ϩ -selective ion channels. Application of cAMP evoked currents in membrane patches of oocytes injected with AtCNGC2 cRNA. Direct activation of the channel by cyclic nucleotide, demonstrated by application of cyclic nucleotide to patches of membranes expressing such channels, is a hallmark characteristic of this ion channel family. Voltage clamp studies (two-electrode configuration) demonstrated that AtCNGC1 and NtCBP4 are also cyclic nucleotidegated channels. Addition of a lipophilic analog of cAMP to the perfusion bath of oocytes injected with NtCBP4 and AtCNGC1 cRNAs induced inward rectified, noninactivating K ϩ currents.Cyclic nucleotide-gated nonselective cation channels (cngcs) represent a newly identified family of plant ion transport proteins (Kö hler et al., 1999;Leng et al., 1999). This putative family of plant ion channels shares deduced secondary and tertiary structural homology with a diverse family of cngcs cloned and characterized from animal systems (Zagotta and Siegelbaum, 1996). However, primary amino acid sequence homology between this family of plant proteins and their presumed animal homologs is not very great (approximately 22%; Leng et al., 1999).Animal cngcs are primarily, but not in all cases (Lee et al., 2001), expressed in sensory neurons and function in signal transduction systems. However, cngcs have been detected in cell types other than sensory receptor neurons, and have been cloned from a number of different tissue types in animals (Biel et al., 1999b;Finn et al., 1996;Lang et al., 2000), suggesting that their role in multicellular organisms may be more diverse than originally thought. Animal cngcs are characterized by the following functional parameters: They are not, or only weakly, voltage gated; they are activated by direct binding of cyclic nucleotide (cAMP and cGMP); they are selective for cations but do not discriminate between conductance of cations such as Ca 2ϩ , Na ϩ , and K ϩ ; their activation by cyclic nucleotides is blocked by calmodulin; and they show varying degrees of conductance rectification (Zagotta and Siegelbaum, 1996). It is interesting that their relative conductance of specific cations, their relative activation by cAMP versus cGMP, and the extent of their conductance rectification are typically related to the specific role they play in a diverse number of signal transduction pathways and, in addition, other physiological processes in animals.Gen...

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“…Some of this work has focused on site-specific mutagenesis of amino acids in the P-region, a highly conserved loop of 21 amino acids present in all cloned K channels (e.g., Yool and Schwarz, 1991;Kirsch et al, 1992;Heginbotham et al, 1994;Kirschet al, 1995). Other efforts have been directed toward experimentally determining aspects of the physical structure of this region (K/irz et al, 1995;Lfi and Miller, 1995;Pascual et al, 1995) or modeling pore structure (Durrell and Guy, 1992;Durrell, 1994,1995;Mackinnon, 1995).…”

Section: Introductionmentioning

confidence: 99%

Unidirectional K+ fluxes through recombinant Shaker potassium channels expressed in single Xenopus oocytes.

Stampe

Begenisich

1996

The Journal of General Physiology

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A B S T R A C T We describe a method to evaluate the ratio of ionic fluxes through recombinant channels expressed in a single Xenopus oocyte. A potassium channel encoded by the Drosophila Shakergene tested by this method exhibited flux ratios far from those expected for independent ion movement. At a fixed extracellular concentration of 25 mM K +, this channel showed single-file diffusion with an Ussing flux-ratio exponent, n', of 3.4 at a membrane potential of -30 mV. There was an apparent, small voltage dependence of this parameter with n' values of 2.4 at -15 and -5 inV. These results indicate that the pore in these channels can simultaneously accommodate at least four K + ions. If each of these K + ions is in contact with two water molecules, the minimum length of the pore is 24 A.

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Mutations in the K+ channel signature sequence

Cited by 784 publications

References 54 publications

sup-9, sup-10, andunc-93May Encode Components of a Two-Pore K⁺Channel that Coordinates Muscle Contraction inCaenorhabditis elegans

sup-9, sup-10, andunc-93May Encode Components of a Two-Pore K⁺Channel that Coordinates Muscle Contraction inCaenorhabditis elegans

Electrophysiological Analysis of Cloned Cyclic Nucleotide-Gated Ion Channels

Unidirectional K+ fluxes through recombinant Shaker potassium channels expressed in single Xenopus oocytes.

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Mutations in the K+ channel signature sequence

Cited by 784 publications

References 54 publications

sup-9, sup-10, andunc-93May Encode Components of a Two-Pore K+Channel that Coordinates Muscle Contraction inCaenorhabditis elegans

sup-9, sup-10, andunc-93May Encode Components of a Two-Pore K+Channel that Coordinates Muscle Contraction inCaenorhabditis elegans

Electrophysiological Analysis of Cloned Cyclic Nucleotide-Gated Ion Channels

Unidirectional K+ fluxes through recombinant Shaker potassium channels expressed in single Xenopus oocytes.

Contact Info

Product

Resources

About

sup-9, sup-10, andunc-93May Encode Components of a Two-Pore K⁺Channel that Coordinates Muscle Contraction inCaenorhabditis elegans

sup-9, sup-10, andunc-93May Encode Components of a Two-Pore K⁺Channel that Coordinates Muscle Contraction inCaenorhabditis elegans