A primate-specific variant of a potassium channel affects cerebral cortex function, cognition, neuronal physiology and risk of having schizophrenia, according to an article published this week in Nature Medicine. The identification of this channel variant provides a new therapeutic target to combat schizophrenia.
Organized neuronal firing is crucial for brain function and is disrupted in schizophrenia. Daniel Weinberger and colleagues have identified a primate-specific, brain-enriched form of the potassium channel KCNH2 that modulates neuronal firing. In the hippocampus, a brain region crucial for cognitive function, the expression of this KCNH2 variant is much higher in people with schizophrenia that in control subjects.
The authors also analyzed 367 families, 1,158 unrelated cases and 1,704 controls subjects and found an association of single nucleotide polymorphisms in KCNH2 with schizophrenia. Risk-associated polymorphisms were indicative of lower intelligence scores and speed of cognitive processing, altered memory and increased hippocampal mRNA levels of the KCNH2 variant.
The authors found that overexpression of the KCNH2 channel variant in neurons induced a rapidly deactivating potassium current that led to high-frequency, persistent neuronal firing that could help explain the neurological abnormalities.