Channelpedia

Kv1.7

Description: potassium voltage-gated channel, shaker-related subfamily, member 7
Gene: Kcna7
Alias: Kv1.7, kcna7, HAK6

Edit - History

Introduction

Kv1.7, encoded by the gene KCNA7, is a member of the potassium voltage-gated channel subfamily A. Kv1.7 plays a central role in cardiac atria repolarization [386]

Experimental data

Rat Kv1.7 gene in CHO host cells       datasheet

Click for details
15 °C
show 123 cells

Click for details
25 °C
show 124 cells

Click for details
35 °C
show 158 cells
Edit - History

Gene

The murine Kv1.7 channels are encoded by the Kcna7 gene, composed of two exons separated by a 1.9-kb intron, and it is located in the mouse chromosome 7 [388].

Species NCBI gene ID Chromosome Position
Human 3743 19 5302
Mouse 16495 7 5422
Rat 365241 1 5492
Edit

Transcript

Species NCBI accession Length (nt)
Human NM_031886.3 4151
Mouse NM_010596.2 3494
Rat NM_001108914.1 3592
Edit

Protein Isoforms

Species Uniprot ID Length (aa)
Human Q96RP8 456
Mouse Q17ST2 489
Rat D4A810 489

Isoforms

Transcript
Length (nt)
Protein
Length (aa)
Variant
Isoform
Edit

Post-Translational Modifications

PTM
Position
Type
Edit - History

Structure

Kv1.7
Visual Representation of Kv1.7 Structure
Methodology for visual representation of structure available here

The N-terminal region of the Kv channels plays important regulatory roles, including inactivation kinetics [593], [594], [595], [557], [596], [597], subunit recognition [598], [599] and redox modulation of the currents flowing through those channels [600], [601]. Hence, the differences among N-terminal regions of Kv channels can result in important functional differences between the different molecular forms of Kv channels. [386].

Kv1.7 Antibody Mechanism of Action

Kv1.3 Kinetics [1650] a highly specific antibody directed against the intracellular N-terminus domain of the Kv1.7 protein. Activity of the antibody was confirmed in mouse samples. The antibody will not recognize the human Kv1.7 protein (Alomone Labs)

STRUCTURE of KV1.7

The deduced mKv1.7 protein consists of 532 amino acids and contains six putative membrane-spanning domains, S1–S6. The hydrophobic core of this protein shares considerable sequence similarity with otherShaker family channels, while the intracellular N and C termini and the external loops between S1/S2 and S3/S4 show little conservation. The protein contains conserved sites for post-translational modifications. As do all other Shaker-related channels, mKv1.7 has a potential tyrosine kinase phosphorylation site (RPSFDAVLY) in its N-terminal region; the proline-rich stretch within the N terminus may be a binding site for SH3 domains of tyrosine kinases. Two protein kinase C consensus sites (Ser/Thr-X-Arg/Lys) are present in the cytoplasmic loop between S4 and S5 of mKv1.7; at least one of these sites is present in all members of the Kv1 family. mKv1.7, like Kv1.6, lacks anN-glycosylation site in the extracellular loop linking the S1 and S2 transmembrane segments; this consensus sequence is conserved in all other Kv1 family genes [388]

Kv1.7 predicted AlphaFold size

Species Area (Å2) Reference
Human 4531.95 source
Mouse 4291.69 source
Rat 5815.45 source

Methodology for AlphaFold size prediction and disclaimer are available here

Edit - History

Kinetics

Kv1.7 Kinetics

Kv1.3 Kinetics [1650] A. Whole-cell current traces. Effect of 1 mM Conk-S1 on currents through hKv1.7 channels expressed in tsA-201 cells evoked by depolarization to 0 or 40 mV (Vh=- 80 mV)

Kinetics in Mouse Heart Muscle

Kv1.3 Kinetics [386]

Kv1.7 channels from mouse heart muscle have two putative translation initiation start sites that generate two channel isoforms with different functional characteristics, mKv1.7L (489 aa) and a shorter mKv1.7S (457 aa). The electrophysiological analysis of mKv1.7L and mKv1.7S channels revealed that the two channel isoforms have different inactivation kinetics. The channel resulting from the longer protein (L) inactivates faster than the shorter channels (S). Our data supports the hypothesis that mKv1.7L channels inactivate predominantly due to an N-type related mechanism, which is impaired in the mKv1.7S form. [386]

Single Channel Current

The mouse Kv1.7 channel is voltage-dependent and rapidly inactivating, exhibits cumulative inactivation, and has a single channel conductance of 21 pS. In an outside-out patch by applying 450-ms voltage ramps from −90 to 80 mV every second, single channel events were seen at potentials more positive than ∼−15 mV [388] Kv1.3 Kinetics [1650]

Kv1.7 currents in tsA-201 cells

Whole-cell current traces were recorded in tsA-201 cells expressing hKv1.7 channels. The currents were evoked by depolarization to 0 mV or to 40mV from a holding voltage of -80mV. Currents facilitated by the human homologue of Kv1.7. resembled those of the mouse short isoform of Kv1.7. [1650]

Edit - History

Expression and Distribution

EXPRESSION IN HUMAN TISSUE

Transcripts of the Kcna7 gene are reported present in several tissues, including strong expression in the heart and skeletal muscle [386] Kv1.7 is also expressed in human the human kidney [1651]

EXPRESSION IN MOUSE

Kcna7 transcripts have been found in the mouse mesenteric artery [602] as well as in the rat main and small pulmonary arteries [603]

A Northern blot of poly(A)+ RNA from mouse heart, brain, spleen, lung, liver, skeletal muscle, kidney, and testis was probed with the mouse Kv1.7-specific 3′-noncoding region sequence [388]

Edit - History

CNS Sub-cellular Distribution

Nephron: Kv1.7 in podocytes

Members of the Kv1 channel family display specific expression patterns in the nephron. Expression of Kv1.7 channels was reported in podocytes [2046]

Beta cells

Kv1.7 channels in the membrane of beta cells plays a role in the repetitive electrical spiking activity needed for glucose-stimulated insulin secretion (GSIS). Kv 1.7 channel contribute to the repolarizing current of beta cells during GSIS [1650]

Edit - History

Function

Neuronal function

mRNAs for Kv1.7 and Kv3.4 are highly abundant in both the atrium and ventricle, which might indicate a functional role of these ion channel subunits in the formation of action potential in the human ventricle and both in the atrium and ventricle, respectively [1652]

Type 2 Diabetes

Conk-S1 increases GSIS in isolated rat islets, likely by reducing Kv1.7-mediated delayed rectifier currents in beta cells, which yields increases in action potential firing and cytoplasmic free calcium. In rats, Conk-S1 increases glucose-dependent insulin secretion without decreasing basal glucose. Thus, we conclude that Kv1.7 contributes to the membrane-repolarizing current of beta cells during GSIS and that block of this specific component of beta cell Kv current offers a potential strategy for enhancing GSIS with minimal risk of hypoglycaemia during metabolic disorders such as Type 2 diabetes [1650]

Cardiac Channel

Characterisation of the human voltage-gated potassium channel gene, KCNA7, a candidate gene for inherited cardiac disorders, and its exclusion as cause of progressive familial heart block I (PFHBI) [387]

Edit - History

Interaction

(Conk-S1),

a naturally occurring cone-snail peptide toxin, Conkunitzin-S1, blocks Kv1.7 channels to provide an intrinsically limited, finely graded control of total beta cell delayed rectifier current and hence of glucose stimulated insulin secretion (GSIS) : 100% washout [1650]

ShK Toxin/Noxiustoxin/Margatoxin

The mKv1.7 channel is also potently blocked by a peptide (ShK toxin) obtained from sea anemone Stichodactyla helianthus(IC50 = 13 nM), and by the scorpion toxins, noxiustoxin (IC50 = 18 nM) and margatoxin (IC50 = 116 nM) [388]

TEA

Kv1.7 is insensitive to tetraethylammonium (because residue is hydrophobic) [388]

charybdotoxin/kaliotoxin

The channel was resistant to charybdotoxin (IC50 >1000 nM) and kaliotoxin (IC50 >1000 nM) [388]

Pharmacology

Pharmacological sensitivity of the mKv1.7 channel were performed, IC50 values in each case being determined when block reached steady-state. The channel was blocked by several non-peptide small molecule antagonists, 4-aminopyridine (IC50 = 245 μM), capsaicin (25 μM), cromakalim (450 μM), tedisamil (18 μM), nifedipine (13 μM), diltiazem (65 μM), and resiniferatoxin (20 μM). Surprisingly, the dihydroquinoline compound, CP-339,818, that blocks rapidly inactivating Kv1 channels in the nanomolar range (30), had little effect on mKv1.7 (IC50 = 10 μM) [388]

Anti-arythmic drugs

amiodarone (Kd=35±muM), flecainide (Kd=8±muM) and quinidine (Kd=15±2 muM). all block kv1.7 [387]

References

386

Finol-Urdaneta RK et al. Molecular and Functional Differences between Heart mKv1.7 Channel Isoforms.
J. Gen. Physiol., 2006 Jul , 128 (133-45).

557

MacKinnon R et al. Functional stoichiometry of Shaker potassium channel inactivation.
Science, 1993 Oct 29 , 262 (757-9).

590

MacDonald PE et al. Members of the Kv1 and Kv2 voltage-dependent K(+) channel families regulate insulin secretion.
Mol. Endocrinol., 2001 Aug , 15 (1423-35).

591

Nerbonne JM Molecular basis of functional voltage-gated K+ channel diversity in the mammalian myocardium.
J. Physiol. (Lond.), 2000 Jun 1 , 525 Pt 2 (285-98).

592

Brown AM Cardiac potassium channels in health and disease.
Trends Cardiovasc. Med., 1997 May , 7 (118-24).

593

Bezanilla F et al. Inactivation of the sodium channel. I. Sodium current experiments.
J. Gen. Physiol., 1977 Nov , 70 (549-66).

594

Hoshi T et al. Biophysical and molecular mechanisms of Shaker potassium channel inactivation.
Science, 1990 Oct 26 , 250 (533-8).

596

Roeper J et al. NIP domain prevents N-type inactivation in voltage-gated potassium channels.
Nature, 1998 Jan 22 , 391 (390-3).

597

Pongs O et al. Functional and molecular aspects of voltage-gated K+ channel beta subunits.
Ann. N. Y. Acad. Sci., 1999 Apr 30 , 868 (344-55).

600

Ruppersberg JP et al. Regulation of fast inactivation of cloned mammalian IK(A) channels by cysteine oxidation.
Nature, 1991 Aug 22 , 352 (711-4).

602

Fountain SJ et al. Functional up-regulation of KCNA gene family expression in murine mesenteric resistance artery smooth muscle.
J. Physiol. (Lond.), 2004 Apr 1 , 556 (29-42).

603

Davies AR et al. Kv channel subunit expression in rat pulmonary arteries.
Lung, 2001 , 179 (147-61).

1650

Finol-Urdaneta RK et al. Block of K(v) 1.7 potassium currents increases glucose-stimulated insulin secretion.
EMBO Mol Med, 2012 May , 4 (424-34).

1652

Ordög B et al. Gene expression profiling of human cardiac potassium and sodium channels.
Int. J. Cardiol., 2006 Aug 28 , 111 (386-93).

2046

Carrisoza-Gaytán R et al. Differential expression of the Kv1 voltage-gated potassium channel family in the rat nephron.
J. Mol. Histol., 2014 Oct , 45 (583-97).

Edit - History

Credits

Contributors: Rajnish Ranjan, Michael Schartner, Nitin Khanna

To cite this page: [Contributors] Channelpedia https://channelpedia.epfl.ch/wikipages/7/ , accessed on 2024 Apr 23


Add section