UNIVERSITY OF MALTA
LIFE SCIENCE RESEARCH SEMINARS
Web: http://www.um.edu.mt/events/scisem/
Email: scisem@um.edu.mt
Abstract form
Title: Potassium channels of the Central Nervous System: from
physiology to disease
Presenter: Prof. Mauro Pessia
Contact address: University of Perugia, Italy
Tel: +39 075 585 7375
Fax: +39 075 585 7371
Email: pessia@unipg.it
Presentation date: 11 October 2010
Abstract
Inwardly rectifying potassium (Kir) channels are found in almost every cell type
where they play key roles in controlling membrane resting potential, cell excitability
and K+ homeostasis. Several Kir clones have been identified so far, forming seven
major subfamilies: Kir1.x–Kir7.x. Important physiological roles have been
established for nearly all of these subfamilies. Kir4.1 channel is a major player in the
astrocyte-mediated regulation of [K+]o in the brain, which is essential for normal
neuronal activity and synaptic functioning. However, the physiological role of the
Kir5.1 channel remains unclear.
Kir5.1 subunit does not produce functional K+ channels when expressed by itself.
Instead it appears to selectively coassemble with Kir4.1 to form novel heteromeric
channels that are highly sensitive to inhibition by intracellular pH and are widely
expressed in several brainstem nuclei including the locus coeruleus (LC). By
generating mutant mice lacking the Kir5.1 (Kcnj16) gene and performing
electrophysiological recordings of LC neurons in brain slices from these mice, we
identify Kir5.1 as an important determinant of PCO2/pH sensitivity in LC neurons and
suggest that Kir5.1 may be involved in the response of these neurons to
hypercapnic acidosis.
KCNJ10, encoding Kir4.1, is a possible candidate gene for Autism Spectrum
Disorders (ASD), and has been linked to seizure susceptibility in humans and mice.
We have investigated whether allelic variations in KCNJ10 are associated with
clinical conditions in which seizures and ASD coexist and identified heterozygous
KCNJ10 mutations in children with ASD, epilepsy, and mental retardation. The
functional characterization of the mutations indicates that gain-of-function defects of
homomeric Kir4.1 and heteromeric Kir4.1/Kir5.1 channels are associated with
autism, susceptibility to seizures, and mental retardation.