Hypoxic modulation of L-type Ca(2+) channels in inspiratory brainstem neurones: intracellular signalling pathways and metabotropic glutamate receptors.
Brief hypoxia (2 min) enhances the activity of L-type Ca(2+) (Ca(L)) channels. The effect is due to glutamate release and concomitant stimulation of metabotropic glutamate receptors of the mGLUR1/5 type [22] [S.L. Mironov, D.W. Richter, L-type Ca(2+) channels in inspiratory neurones and their modulation by hypoxia, J. Physiol. 512 (1998) 75-87.]. Besides increasing single channel activity, hypoxia induces a negative shift of the activation curve and slows down the inactivation of the Ca(L) current. In the present study we investigated these effects further, aiming to reveal intracellular signalling pathways that mediate the coupling between mGLURs and Ca(L) channels. Channel activity was recorded in cell-attached patches from inspiratory brainstem neurones of neonatal mice (P6-11). Ca(L) channels were inhibited by the mGluR2/3 agonists. mGluR1/5 agonists accelerated and mGluR2/3 agonists suppressed the respiratory output, and correspondingly modified the hypoxic response of the respiratory center. Ca(L) channels were also modulated by protein kinase C, but this did not prevent the hypoxic modification of channel activity. G-protein activators enhanced and G-protein inhibitors suppressed the Ca(L) channel activity, and in the presence of these agents the effects of hypoxia were abolished. Ryanodine but not thapsigargin inhibited the channel activity and occluded the hypoxic potentiation. Only G-protein-specific agents and ryanodine prevented the slowing down of inactivation induced by hypoxia. Our data indicate that coupling between mGluR1/5 and Ca(L) channels is mediated by pathways that utilize G-proteins and ryanodine receptors. Glutamate release and concomitant activation of Ca(L) channels are responsible for accelerating of respiratory rhythm during early hypoxia.[1]References
- Hypoxic modulation of L-type Ca(2+) channels in inspiratory brainstem neurones: intracellular signalling pathways and metabotropic glutamate receptors. Mironov, S.L., Richter, D.W. Brain Res. (2000) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
