Hypercapnia Inhibits Both Transient and Sustained Potassium Currents in Chemosensitive Neurons from Neonatal Rat Locus Coeruleus (LC)

Increased ventilation is stimulated by an increase in CO ₂ /H ⁺ , which is detected by peripheral chemoreceptors and central chemosensitive neurons. We studied CO ₂ /H ⁺ -sensitive K ⁺ channels in rat LC neurons. We hypothesize that multiple ion channels are involved in the neuronal response to changes in CO ₂ /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% CO ₂ 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 Cd ²⁺ (200 µm) to block Na ⁺ and Ca ²⁺ 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% CO ₂ , 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.