Neuronal mechanisms mediating the integration of respiratory responses to hypoxia

The activation of peripheral chemoreceptors by hypoxia or electrical stimul ation of the carotid sinus nerve elicited a hypoxic respiratory response co nsisting of both stimulatory and subsequent or simultaneous inhibitory comp onents (hypoxic respiratory stimulation and depression). Both components ha ve different time domains of responses (time-dependent response), providing an integrated respiratory response to hypoxia, This review has focused on the neuroanatomical and neurophysiological correlations responsible for the se responses and their neuropharmacological mechanisms. Hypoxic respiratory depression is characterized by the initial activation of respiration follo wed by a progressive and gradual decline in ventilation during prolonged an d/or severe hypoxic exposure (biphasic response). The responsible mechanism s for the depression are located within the central nervous system and may be dependent upon activity from peripheral chemoreceptor, Two underlying me chanisms contributing to the depression have been advocated. (1) Change in synaptic transmission: Within the neuronal network controlling the hypoxic respiratory response, hypoxia might induce the enhancement of inhibitory ne urotransmission (modulation), disfacilitation of excitatory neurotransmissi on or both. (2) Change in the membrane property of respiratory neurons: Hyp oxia might suppress the membrane excitability of respiratory neurons compos ing the hypoxic respiratory response via modulating ion channels, leading t o hyperpolarization or depolarization blocking of the neurons. However, the quantitative aspects of PaO2 (degree and duration of hypoxic exposure) to induce these changes and the susceptibility of both mechanisms to the PaO2 level have not yet been clearly elucidated.