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Excitatory peptides and osmotic pressure modulate mechanosensitive cation channels in concert

Nature Neuroscience volume 3, pages 572–579 (2000)Cite this article

Abstract

Behavioral and neuroendocrine responses underlying systemic osmoregulation are synergistically controlled by osmoreceptors and neuropeptides released within the hypothalamus. Although mechanisms underlying osmoreception are understood, the cellular basis for the integration of osmotic and peptidergic signals remains unknown. Here we show that the excitatory effects of angiotensin II, cholecystokinin and neurotensin on supraoptic neurosecretory neurons are due to the stimulation of the stretch-inactivated cation channels responsible for osmoreception. This molecular convergence underlies the facilitatory effects of neuropeptides on responses to osmotic stimulation and provides a basis for the gating effects of plasma osmolality on the responsiveness of osmoregulatory neurons to peptidergic stimulation.

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Figure 1: Peptidergic excitation of MNCs.
Figure 2: Peptide actions on single-channel activity.
Figure 3: Channel kinetics during peptidergic stimulation.
Figure 4: Excitatory peptides convergently regulate 35 pS cation channels in MNCs.
Figure 5: Excitatory peptides stimulate stretch-inactivated cation channels in MNCs.
Figure 6: Effects of Gd3+ on responses to peptidergic stimulation.
Figure 7: Interactions between osmotic and peptidergic stimuli in hypothalamic MNCs.

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Acknowledgements

This work was supported by an operating grant and Senior Scientist award to C.W.B. from the Medical Research Council of Canada. We thank S.H.R. Oliet for comments during the preparation of this manuscript.

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  1. Yassar Chakfe

    Present address: Montreal Neurological Institute, 3801 University Street, Montreal, Quebec, H3A 2B4, Canada

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  1. Centre for Research In Neuroscience, Montreal General Hospital and McGill University, 1650 Cedar Avenue, Montreal, H3G 1A4, Quebec, Canada

    Yassar Chakfe & Charles W. Bourque

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Correspondence to Charles W. Bourque.

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Chakfe, Y., Bourque, C. Excitatory peptides and osmotic pressure modulate mechanosensitive cation channels in concert. Nat Neurosci 3, 572–579 (2000). https://doi.org/10.1038/75744

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