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EXERCISE AND RESPIRATORY PHYSIOLOGY

Heme oxygenase is necessary for the excitatory response of cultured neonatal rat rostral ventrolateral medulla neurons to hypoxia

Division of Pulmonary and Critical Care Medicine, Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey

Submitted 29 March 2008 ; accepted in final form 21 October 2008

Heme oxygenase has been linked to the oxygen-sensing function of the carotid body, pulmonary vasculature, cerebral vasculature, and airway smooth muscle. We have shown previously that the cardiorespiratory regions of the rostral ventrolateral medulla are excited by local hypoxia and that heme oxygenase-2 (HO-2) is expressed in the hypoxia-chemosensitive regions of the rostral ventrolateral medulla (RVLM), the respiratory pre-Bötzinger complex, and C1 sympathoexcitatory region. To determine whether heme oxygenase is necessary for the hypoxic-excitation of dissociated RVLM neurons (P1) cultured on confluent medullary astrocytes (P5), we examined their electrophysiological responses to hypoxia (NaCN and low PO₂) using the whole-cell perforated patch clamp technique before and after blocking heme oxygenase with tin protoporphyrin-IX (SnPP-IX). Following the electrophysiological recording, immunocytochemistry was performed on the recorded neuron to correlate the electrophysiological response to hypoxia with the expression of HO-2. We found that the responses to NaCN and hypoxia were similar. RVLM neurons responded to NaCN and low PO₂ with either depolarization or hyperpolarization and SnPP-IX blocked the depolarization response of hypoxia-excited neurons to both NaCN and low PO₂ but had no effect on the hyperpolarization response of hypoxia-depressed neurons. Consistent with this observation, HO-2 expression was present only in the hypoxia-excited neurons. We conclude that RVLM neurons are excited by hypoxia via a heme oxygenase-dependent mechanism.

chemosensitivity; pre-Bötzinger complex; C1 sympathoexcitatory region

This article has been cited by other articles:

				J. Sunderram, J. Semmlow, S. Thakker-Varia, M. Bhaumik, O. Hoang-Le, and J. A. Neubauer Heme oxygenase-1-dependent central cardiorespiratory adaptations to chronic hypoxia in mice Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2009; 297(2): R300 - R312. [Abstract] [Full Text] [PDF]

				F. L. Powell Heme oxygenase is necessary for the excitatory response of cultured neonatal rat rostral ventrolateral medulla neurons to hypoxia by D'Agostino D, Mazza E, and Neubauer JA Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2009; 296(1): R100 - R101. [Full Text] [PDF]