Increased ventilation is stimulated by an increase in CO2/H+, which is detected by peripheral chemoreceptors and central chemosensitive neurons. We studied CO2/H+-sensitive K+ channels in rat LC neurons. We hypothesize that multiple ion channels are involved in the neuronal response to changes in CO2/H+, with K+ channels being an important component mediating this response. In this study, we used whole cell voltage clamp to test the effect of 15% CO2 on both transient and sustained K+ currents of LC neurons from neonatal rat brain slices. Neurons were clamped at -80mV. Voltage-dependent K+ currents were evoked by various depolarizing pulses (300 ms duration) in 10 mV increments from -100mV to 50mV in the presence of TTX (1 µm) and Cd2+ (200 µm) to block Na+ and Ca2+channels, respectively. Transient K+ currents were inhibited by 4-amino pyridine (4-AP; 5mM) and sustained K+ currents were inhibited by tetraethylammonium (TEA; 20mM). Five minutes after perfusion with aCSF equilibrated with 15% CO2, the conductances of both transient and sustained K+ channels were decreased by 28 ± 9.5% (n=3) and 19 ± 9.6% (n=3), respectively. These results support the hypothesis that hypercapnia increases the firing frequency of LC neurons through depolarization due to inhibition of multiple K+ channels, including transient and sustained K+ conductances.

Supported by NIH Grant R01-HL56683-11.