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The Journal of Neuroscience, September 17, 2008, 28(38):9536-9544; doi:10.1523/JNEUROSCI.1495-08.2008

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Cellular/Molecular
Amplification of Transducer Gain by Angiotensin II-Mediated Enhancement of Cortical Actin Density in Osmosensory Neurons

Zizhen Zhang and Charles W. Bourque

Centre for Research in Neuroscience, McGill University and Montreal General Hospital, Montreal, Quebec, Canada H3G 1A4

Correspondence should be addressed to Dr. Charles W. Bourque, Division of Neurology, Montreal General Hospital, 1650 Cedar Avenue, Room L7-216, Montreal, Quebec, Canada H3G 1A4. Email: charles.bourque{at}mcgill.ca

Osmosensory neurons transduce osmotic signals into a neural spike code that commands behavioral and endocrine responses that mediate body fluid homeostasis. Although changes in osmoregulatory reflex gain are known to occur under physiological and pathological conditions, the basis for this modulation is unknown. Here, we show that angiotensin II amplifies osmosensory transduction by enhancing the proportional relationship between osmolality, receptor potential, and action potential firing in rat supraoptic nucleus neurons. This effect is mediated by a phospholipase C- and protein kinase C-dependent increase in cellular mechanosensitivity that is associated with a rapid increase in cortical actin filament density. Preventing this increase with cytochalasin D eliminated the enhancement of mechanosensitivity, whereas enhancing actin filament density with jasplakinolide potentiated mechanosensitivity and occluded the effects of angiotensin II. These results indicate that a receptor-mediated increase in cortical actin density can enhance osmosensitivity in acutely isolated supraoptic neurons.

Key words: actin; angiotensin II; cytoskeleton; osmotic pressure; osmosensitivity; supraoptic nucleus; vasopressin

Received April 7, 2008; revised July 31, 2008; accepted Aug. 18, 2008.

Correspondence should be addressed to Dr. Charles W. Bourque, Division of Neurology, Montreal General Hospital, 1650 Cedar Avenue, Room L7-216, Montreal, Quebec, Canada H3G 1A4. Email: charles.bourque{at}mcgill.ca






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