Juan Carlos Sáez, Ph.D. Department of Cell Physiology & Molecular Biophysics

Department of Cell Physiology & Molecular Biophysics
Seminar Series
Juan Carlos Sáez, Ph.D.
Department of Physiology
Facultad de Ciencias Biologicas
Pontificia Univ. Católica de Chile
Santiago, Chile
Room 5BC201, 10:00 – 11:00 a.m., January 22, 2009
“Astroglial hemichannels and gap junction channels in in
vitro models of neurodegenerative diseases”
In normal central nervous system, neurons and astrocytes, the most abundant cells, express
pannexins and connexins, which form gap-junctional channels and hemichannels. It seems that in
mammals, native pannexins form only hemichannels whereas connexins form both gapjunctional channels and hemichannels. Gap-junctional channels connect the cytoplasms of
contacting cells and coordinate their electric and metabolic activity. Hemichannels communicate
the intra- and extracellular compartments, serving as a diffusional pathway for ions and small
molecules. A subthreshold stimulation of hemichannels by acute pathological threatening
conditions (e.g., global ischemia) enhances neuronal Cx36 and glial Cx43 hemichannel activity,
favoring ATP release and generation of preconditioning. If the stimulus is deleterious, microglia
become overactivated and release bioactive molecules that increase the activity of hemichannels
and reduce gap-junctional communication in astroglial networks, depriving neurons of astrocytic
protective functions, further reducing neuronal viability. In several neurodegenerative diseases,
continuous glial activation triggered by low levels of anomalous proteins induces glial
hemichannel and gap-junctional channel disorders similar to those of acute inflammatory
responses triggered by ischemia or infectious diseases. These changes are likely to occur in
diverse cell types of the CNS and contribute to neurodegeneration during inflammatory process.
Retamal MA, Cortés CJ, Reuss L, Bennett MVL and Sáez JC (2006) S-nitrosylation and permeation
through connexin 43 hemichannels in astrocytes: induction by oxidant stress and reversal by reducing
agents. Proc Natl Acad Sci USA 103, 4475-4480.
Retamal MA, Schalper KA, Shoji KJ, Orellana JA, Bennett MVL and Sáez JC (2007) Possible
involvement of different connexin43 domains in plasma membrane permeabilization induced by
ischemia-reperfusion. J Membr Biol. 218, 49-63.
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Department of Physiology: Crystal Perkins
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