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 Po(2)) 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 Po(2) with either depolarization or hyperpolarization and
SnPP-IX blocked the depolarization response of
hypoxia-excited neurons to both NaCN and low Po(2) 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.