The Response of Membrane Potential (Vm) and Intracellular pH (pHi) to Hypercapnia in Neurons and Astrocytes from Rat Retrotrapezoid Nucleus (RTN)

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We compared the response to hypercapnia (10%) in both neurons and astrocytes between a distinct area of the retrotrapezoid nucleus (RTN), the medio-caudal RTN (mcRTN) and more intermediate and rostral RTN areas (irRTN) in medullary brain slices from neonatal rats. Exposure to hypercapnic acidosis (HA) caused pHo to decline from 7.45 to 7.15 and caused a maintained, intracellular acidification of 0.15±0.02 pH unit in 90% of neurons from both areas of the RTN (n=16). HA excited 44% of mcRTN (7 of 16) and 38% of irRTN neurons (6 of 16), increasing firing rate by 167±75% (chemosensitivity index, CI, of 256±72%) and 310±93% (CI of 292±50%) respectively. These responses did not vary throughout neonatal development. We investigated the role of pHo by comparing the responses between HA (decreased pHi and pHo) and isohydric hypercapnia (IH; decreased pHi with constant pHo) in mcRTN neurons. Neurons excited by HA (firing rate increased by 156±46%; n=5) were excited to the same extent by IH (firing rate increased by 167±38%; n=5). Neurons insensitive to HA were also insensitive to IH. In astrocytes from both areas of the RTN, exposure to HA caused a maintained, intracellular acidification of 0.17±0.02 pH unit (n=6) and a depolarization of 5±1mV (n=12). In summary, a high percentage of neurons (42%) from the entire RTN are highly responsive (CI 248%) to HA; this may reflect both synaptically driven and intrinsic mechanisms of CO2 sensitivity. Changes of pHi appear to be a more significant stimulus than changes of pHo in chemosensory RTN neurons. Finally, the lack of astrocytic pHi regulation in response to HA suggests that astrocytes do not enhance extracellular acidification during hypercapnia in the RTN in the neonatal period.