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 .

R01 NS069842-01 NINDS NIH HHS , R01 NS069842-02 NINDS NIH HHS , R01 NS069842-03 NINDS NIH HHS , R21 NS057000-01 NINDS NIH HHS , R01 NS069842-04 NINDS NIH HHS , R01 NS069842 NINDS NIH HHS , R21 NS057000 NINDS NIH HHS

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).

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