Hypercapnia Inhibits Both Transient and Sustained Potassium Currents in Chemosensitive Neurons from Neonatal Rat Locus Coeruleus (LC)
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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.
& Putnam, R. W.
(2009). Hypercapnia Inhibits Both Transient and Sustained Potassium Currents in Chemosensitive Neurons from Neonatal Rat Locus Coeruleus (LC). The FASEB Journal, 23 (Meeting Abstract Supplement).
Presented at the 2009 Federation of American Societies for Experimental Biology (FASEB) Science Research Conference.
Presentation Number 621.5.