Description: potassium voltage gated channel, shaker related subfamily, member 6
Gene: Kcna6
Alias: Kv1.6, kcna6, MK1.6

Edit - History


The gene KCNA6 encodes Kv1.6 (alos known as HBK2; KV1.6; FLJ25134), a member of the potassium channel, voltage-gated, shaker-related subfamily. This member contains six membrane-spanning domains with a shaker-type repeat in the fourth segment. These subunits also behave as ‘delayed rectifiers’ in homomeric assemblies, activating at-50 mV, with half activation at -20 mV. The coding region of this gene is intronless, and the gene is clustered with genes KCNA1 and KCNA5 on chromosome 12.

Experimental data



Species NCBI gene ID Chromosome Position
Human 3742 12 41778
Mouse 16494 6 32506
Rat 64358 4 33248



Species NCBI accession Length (nt)
Human NM_002235.5 3985
Mouse NM_013568.6 5853
Rat NM_023954.2 6696


Protein Isoforms

Species Uniprot ID Length (aa)
Human P17658 529
Mouse Q61923 529
Rat P17659 530


Length (nt)
Length (aa)


Post-Translational Modifications


Edit - History


Crystal Structure

Kv1.5 Three homology models for the complex pl14a-Kv1.6 (models I-III). Space filling representation of pl14a, all four Arg represented in blue (Arg3, Arg5, Arg12 and Arg25), the residue Lys18 is shown in orange, whereas the four domains of the Kv1.6 channel are represented in ribbon with four different colors. Conotoxin pl14a is a complete blockers of Kv1.6 [1619]

Kv1.5 The structural features cor- responded to those defined in the crystallographic structure of the Shaker T1 domain (10) are indicated. The polypeptide backbones belonging to the α- helix, β-strand, turn and random coil regions are shown in red, yellow, blue and green, respectively. The backbone RMSDs of Kv1.4 and Kv1.6 after super- imposing the homology models to the crystallographic structure of Shaker are given on the top right corner of each model [1662]

Edit - History


Kv1.6 kinetics


In vitro expression of this channel produces an outward current with an activation threshold around 240 mV and little inactivation during a 200 ms pulse [1620]

Voltage-gated K channels, Kvl.1, Kvl.4, Kvl.5, and Kvl.6, cloned from rat brain and expressed in Xenopus oocytes have similar activation and deactivation kinetics. [431]

The single-channel conduc- tance of Kv1.4 is much smaller than that of either Kv1.1 or Kv1.6 [1621]

Kv1.6 currents measured in Xenopus oocytes and effect of Bcstx2

Xenopus oocytes expressing Kv1.6 channels were used to record whole-cell currents. After 500 ms depolarizations to 0 mV, a 500 ms pulse to −50 mV was used to induce IR currents, from a holding potential of −90 mV. The scorpion toxin Bcstx2 potently inhibited rKv1.6 currents.[2043]



Model Kv1.6 (ID=22)      

CellType oocyte
Age 0 Days
Reversal -65.0 mV
Ion K +
Ligand ion
Reference [276] O Pongs et. al; EMBO J. 1990 Jun
mpower 1.0
m Inf 1/(1+exp(((v -(-20.800))/(-8.100))))
m Tau 30.000/(1+exp(((v -(-46.560))/(44.140))))
hpower 1.0
h Inf 1/(1+exp(((v -(-22.000))/(11.390))))
h Tau 5000.000/(1+exp(((v -(-46.560))/(-44.140))))

MOD - xml - channelML

Edit - History

Expression and Distribution

Kv1.6 appeared uniform throughout the bovine brain. Kv-specific antibody precipitated a different proportion (anti-Kvl.2 > 1.1 >> 1.6 > 1.4) of the channels detectable with radioiodinated alpha-DTX in every brain region.[432]

Kv1.6 was found in human cardiac fibroblasts, besides more numerous other ion-channels [428] and also in in murine colon myocytes [430].

All the a-subunits of Kv1.1–Kv1.6 channels were found to be expressed in the ganglion cell layer (GCL) of the rat retina at postnatal day 5 (P5). The GCL expressed Kv1.6 channels already at P1 at high levels. Their expression upregulates postnatally and the pattern and distribution change in an isoform-specific manner.[429]

Kv1.6 transcript was found in astrocyte cultures at a level approximately 65% in primary cultures and 16% in secondary cultures of the level found in adult mouse brain [1620]

Edit - History

CNS Sub-cellular Distribution


Immunohistochemistry confirms that Kv1.1 and Kv1.2 (ILTS channels), but not Kv1.6, are concentrated in the first 20 um of the medial nucleus of the trapezoid body axons. Kv1.6 immunofluorescence showed somatic but not axonal staining was observed (n= 4 animals) [1704]

Subunit-specific trafficking

Kv1 channels are trafficked in a subunit-specific manner. Kv1.6 is predominantly localized to the endoplasmic reticulum in astrocytes while Kv1.3 is localized to the cis-Golgi [1978]

Edit - History


Excitability of Sensory Neurons

Potassium channels Kv1.1, Kv1.2 and Kv1.6 influence excitability of rat visceral sensory neurons [1792]

A modification of the biophysical properties of Kv1.6-induced K+ current is triggered by the expression level of Kv1.6 channel in the cell membrane. The inactivation properties are close to canonical C-type inactivation.[11]

Synaptic Transmission

Besides being responsible for cell membrane repolarization after initiation of an action potential, Kv1.6 - like other voltage-gated K+ channels - is known to modulate synaptic transmission and secretion from endocrine cells, such as insulin from pancreatic islet cells [590]. The basic electrophysiological characteristics (i.e., kinetics) of Kv channels contribute importantly to the modulation of the shape, frequency, and duration of the cardiac action potential [591], [592].

The fast N-type inactivation endowed by Kv1.4 can be prevented by the presence of Kv1.6 through its NIP (N-type inactivation prevention) domain, giving rise to a much slower inactivating/sustained K+ current [380]


Amyotrophic Lateral Sclerosis

CSF from Amyotrophic Lateral Sclerosis (ALS) patients (ALS-CSF) has the potential to perturb ion channel expression, specifically the Na(v)1.6, and K(v)1.6 channels in newborn rat spinal motor neurons both in vivo and in vitro. A decrease in the expression of Na(v)1.6 and K(v)1.6 channels in motor neurons in ALS-CSF treated group, and the presence of trophic factors like Brain Derived Neurotrophic Factor (BDNF) and Ciliary Neurotrophic Factor CNTF partially reversed the effects produced by ALS-CSF [381]


Kv channels might be involved in the failure of polymodal nociceptive C-fibers associated with diabetic hyperalgesia. α-Dendrotoxin (α-DTX) down-regulates Kv1.2 and Kv1.6 channel currrents in small dorsal root ganglion neurons and C-fibers. Malfunction of α-DTX-sensitive Kv1 channels may therefore be involved in the hyperexcitability of these neurons [1934]


The cholinergic regulation of arterial luminal diameter involves a functionally relevant role of Kv1.6 channels. Kv1.6 channels were localized exclusively in the smooth muscle cells of the mouse ophthalmic artery [2045]

Edit - History




Kv1.4 channels are more sensitive to block by internal Mg2+ at low depolarizations than either Kv1.1 or Kv1.6.



The mutation of Kv1.4K533 at the putative outer mouth of the pore to Y, the equivalent residue in Kv1.1, has already been shown to greatly increase the sensitivity of Kv1.4 channels to external TEA+, such that it is the same as that of Kv1.1. We have now found that substitu- tion of the corresponding tyrosine (Y430) in Kv1.6 by lysine produces, as expected from the effect of the con- verse mutation in Kv1.4, a massive (at least 35-fold) de- crease in the sensitivity of Kv1.6 channels to external TEA+


Strontium (Sr2+; 7-50 mM) effects Kv1.6 (from rat, expressed in Xenopus oocytes) in so far as the K+ conductance curve is shifted along the potential axis, where the shift of Kv1.6 lies between that of Kv1.1, was shifted most and Kv3.4, least, 21 and 8 mV, respectively, at 50 raM. [12]


Subunit ordering of Kv1 channels influences their properties: N-type rapid deactivation of Kv1.4 containing channels is over-ridden when Kv1.6 subunits are adjacent to the Kv1.4 subunit. Placing Kv1.4 and Kv1.6 genes together, followed by two copies of Kv1.2, prevents the K+ current from fast inactivation. In contrast, separating Kv1.4 and Kv1.6 by a copy of Kv1.2 genes between them, fast inactivation is prevented again.[380]


Kvbeta3 confered a rapid inactivation to Kv1.6 channels. Kv1.6 channels that possess an N-type inactivation prevention (NIP) domain for Kvbeta1.1, inactivated rapidly when co-expressed with Kvbeta3. [390]



The dendrotoxins have little or no anti-protease activity, but they were demonstrated to block particular subtypes of voltage-dependent potassium channels in neurons. Studies with cloned K(+) channels indicate that alpha-dendrotoxin from green mamba Dendroaspis angusticeps blocks Kv1.1, Kv1.2 and Kv1.6 channels in the nano molar range [1618]

Toxin Blockers

Charybdotoxin, margatoxin and hongotoxin inhibit Kv1.6 in the low nM range. Another scorpion toxin, tamulustoxin (from the indian red scorpion, Methobuthus tamales) has been recently identified as a blocker of Kv1.6 channels expressed in CHO cells.


pl14a in X oocytes

Kv1.5 We isolated and characterized a conotoxin from the Indo-Pacific worm-hunting cone C. Using the oocyte heterologous expression system, pl14a was shown to inhibit both a K+ channel subtype (Kv1.6, IC50 = 1.59 μM) [1661]

Sea anemone toxin BcsTx2

Sea anemone neurotoxins can be useful to elucidate the function of voltage-gated K+ channels (KV). A comparitive study of novel Kv1 channel toxins demostrated that BcsTx1 shows high affinity for rKv1.2 while BcsTx2 potently blocked rKv1.6 [2043]



Guihard G et al. Human Kv1.6 current displays a C-type-like inactivation when re-expressed in cos-7 cells.
Biochem. Biophys. Res. Commun., 2003 Nov 7 , 311 (83-9).


Harvey AL Twenty years of dendrotoxins.
Toxicon, 2001 Jan , 39 (15-26).

Mondal S et al. In silico detection of binding mode of J-superfamily conotoxin pl14a with Kv1.6 channel.
In Silico Biol. (Gedrukt), 2007 , 7 (175-86).

Gómez-Hernandez JM et al. Molecular basis for different pore properties of potassium channels from the rat brain Kv1 gene family.
Pflugers Arch., 1997 Nov , 434 (661-8).

Dodson PD et al. Two heteromeric Kv1 potassium channels differentially regulate action potential firing.
J. Neurosci., 2002 Aug 15 , 22 (6953-61).

Glazebrook PA et al. Potassium channels Kv1.1, Kv1.2 and Kv1.6 influence excitability of rat visceral sensory neurons.
J. Physiol. (Lond.), 2002 Jun 1 , 541 (467-82).

Edit - History


Contributors: Rajnish Ranjan, Michael Schartner, Nitin Khanna

To cite this page: [Contributors] Channelpedia , accessed on [date]