Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Deletion of the potassium channel Kv12.2 causes hippocampal hyperexcitability and epilepsy.
Zhang X
,
Bertaso F
,
Yoo JW
,
Baumgärtel K
,
Clancy SM
,
Lee V
,
Cienfuegos C
,
Wilmot C
,
Avis J
,
Hunyh T
,
Daguia C
,
Schmedt C
,
Noebels J
,
Jegla T
.
???displayArticle.abstract???
We found the voltage-gated K+ channel Kv12.2 to be a potent regulator of excitability in hippocampal pyramidal neurons. Genetic deletion and pharmacologic block of Kv12.2 substantially reduced the firing threshold of these neurons. Kv12.2-/- (also known as Kcnh3-/-) mice showed signs of persistent neuronal hyperexcitability including frequent interictal spiking, spontaneous seizures and increased sensitivity to the chemoconvulsant pentylenetetrazol.
Figure 2. Pharmacological block of Kv12.2 increases neuronal excitability(a) The Kv12.2 inhibitor CX4 blocks steady state K+ current at −20 mV in Kv12.2+/+ but not Kv12.2−/− hippocampal pyramidal neurons cultured at P2. We used 10 μM XE991 to block the M-current. (b–d) Resting membrane potential of Kv12.2+/+ but not Kv12.2−/− neurons depolarized during CX4 application. The depolarization in Kv12.2+/+ neurons is accompanied by an increase in firing (b, arrow); Kv12.2−/− neurons (c) typically had high spontaneous firing rates that were not affected by CX4. Baseline resting potentials in (b) and (c) are indicated with dotted lines. Values in d are mean ± s.e.m.; asterisks indicate significance (p < 0.05); n = 8–20.
Figure 3. Kv12.2−/− seizure phenotypes(a–c) Frequent generalized interictal spikes were detected in EEG recordings from Kv12.2−/− and Kv12.2+/− but not Kv12.2+/+ mice. (d) EEG recording of a seizure in a Kv12.2−/− mouse. Letters indicate recording electrode position: L (left), R (right), F (frontal), T (temporal) and P (parietal). (e) Latency to seizure (mean ± s.e.m., significance = *, p < 0.01, n = 15–18) and (f) seizure severity following intraperitoneal injection of 40 or 50 mg/Kg PTZ. Seizure phases were scored as reduced motility and prostrate position (1), partial clonus (2), generalized clonus involving the extremities (3), and tonic–clonic seizure with rigid paw extension (4). Heterozygotes had increased seizure severity at the 40 mg/Kg dose (inset, n = 9).
Becchetti,
The functional properties of the human ether-à-go-go-like (HELK2) K+ channel.
2002, Pubmed
Becchetti,
The functional properties of the human ether-à-go-go-like (HELK2) K+ channel.
2002,
Pubmed
Ho,
Genetic analysis of Mint/X11 proteins: essential presynaptic functions of a neuronal adaptor protein family.
2006,
Pubmed
Holmes,
Animal model studies application to human patients.
2007,
Pubmed
Jegla,
Evolution of the human ion channel set.
2009,
Pubmed
Kim,
Modality-specific retrograde amnesia of fear.
1992,
Pubmed
McCormick,
On the cellular and network bases of epileptic seizures.
2001,
Pubmed
Miyake,
Disruption of the ether-a-go-go K+ channel gene BEC1/KCNH3 enhances cognitive function.
2009,
Pubmed
Noebels,
The biology of epilepsy genes.
2003,
Pubmed
Nolan,
The hyperpolarization-activated HCN1 channel is important for motor learning and neuronal integration by cerebellar Purkinje cells.
2003,
Pubmed
Peters,
Conditional transgenic suppression of M channels in mouse brain reveals functions in neuronal excitability, resonance and behavior.
2005,
Pubmed
,
Xenbase
Putnam,
Sea anemone genome reveals ancestral eumetazoan gene repertoire and genomic organization.
2007,
Pubmed
Saganich,
Differential expression of genes encoding subthreshold-operating voltage-gated K+ channels in brain.
2001,
Pubmed
Srivastava,
The Trichoplax genome and the nature of placozoans.
2008,
Pubmed
Streng,
Open-field behavior in four inbred mouse strains.
1971,
Pubmed
Trudeau,
Functional analysis of a mouse brain Elk-type K+ channel.
1999,
Pubmed
,
Xenbase
