Mitochondrial K ATP channels in respiratory neurons and their role in the hypoxic facilitation of rhythmic activity

• Published in: Brain research Vol. 1033; no. 1; pp. 20 - 27
• Main Authors: Mironov, S.L., Hartelt, N., Ivannikov, M.V.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.02.2005
• Subjects: Ca 2; Hypoxic facilitation; K ATP channels; Mitochondria; PKC; Excitable membranes and synaptic transmission; Hypoxic facilitation; BDNF; PMA; LTP; PKC; ACSF; mK ATP; 5-HD; K ATP channels; Ca 2; pBC; Mitochondria; pK ATP; HT 2a
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2004.11.011

Hypoxia is damaging in neurons, but it can also produce beneficial effects by consolidating the activity of neural networks such as facilitation of respiratory activity [T.L. Baker-Herman, D.D. Fuller, R.W. Bavis, A.G. Zabka, F.J. Golder, N.J. Doperalski, R.A. Johnson, J.J. Watters, G.S. Mitchell, Nature Neuroscience 7 (2004) 48–55; J.L. Feldman, G.S. Mitchell, E.E. Nattie, Ann. Rev. Neurosci. 26 (2003) 239–266; D.M. Blitz, J.M. Ramirez, J. Neurophysiol. 87 (2002) 2964–2971]. The underlying mechanisms are unknown, and we hypothesized they may be similar to ischemic preconditioning in the heart, involving mitochondrial K ATP (mK ATP) channels. By measuring the mitochondrial potential ( Ψ m) and Ca 2+ ([Ca 2+] m) in neurons of pre-Bötzinger complex (pBC), we examined the functional expression of mK ATP channels in the respiratory network. The opener of mK ATP channels diazoxide decreased Ψ m and [Ca 2+] m both in pBC neurons and in isolated immobilized mitochondria. 5-Hydroxydecanoate (5-HD), the blocker of mK ATP channels, increased both Ψ m and [Ca 2+] m. Phorbol 12-myristate-13-acetate (PMA) mimicked the effects of diazoxide. Protein kinase C (PKC) was stimulated during hypoxia that occurred mostly at the mitochondria. Brief hypoxia induced facilitation of the respiratory activity, which was prevented after blockade of mK ATP channels with 5-HD and PKC with staurosporine. Diazoxide potentiated the motor output and subsequent application of hypoxia was ineffective. We propose that a PKC-induced stimulation of K ATP channels in the mitochondria of respiratory neurons is responsible for the hypoxic facilitation of rhythmic activity.