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.