Sodium and Calcium Current-Mediated Pacemaker Neurons and Respiratory Rhythm Generation

C. A. Del Negro
2005 Journal of Neuroscience  
The breathing motor pattern in mammals originates in brainstem networks. Whether pacemaker neurons play an obligatory role remains a key unanswered question. We performed whole-cell recordings in the preBötzinger Complex in slice preparations from neonatal rodents and tested for pacemaker activity. We observed persistent Na ϩ current (I NaP )-mediated bursting in ϳ5% of inspiratory neurons in postnatal day 0 (P0)-P5 and in P8 -P10 slices. I NaP -mediated bursting was voltage dependent and
more » ... dependent and blocked by 20 M riluzole (RIL). We found Ca 2ϩ current (I Ca )-dependent bursting in 7.5% of inspiratory neurons in P8 -P10 slices, but in P0 -P5 slices these cells were exceedingly rare (0.6%). This bursting was voltage independent and blocked by 100 M Cd 2ϩ or flufenamic acid (FFA) (10 -200 M), which suggests that a Ca 2ϩ -activated inward cationic current (I CAN ) underlies burst generation. These data substantiate our observation that P0 -P5 slices exposed to RIL contain few (if any) pacemaker neurons, yet maintain respiratory rhythm. We also show that 20 nM TTX or coapplication of 20 M RIL ϩ FFA (100 -200 M) stops the respiratory rhythm, but that adding 2 M substance P restarts it. We conclude that I NaP and I CAN enhance neuronal excitability and promote rhythmogenesis, even if their magnitude is insufficient to support bursting-pacemaker activity in individual neurons. When I NaP and I CAN are removed pharmacologically, the rhythm can be maintained by boosting neural excitability, which is inconsistent with a pacemaker-essential mechanism of respiratory rhythmogenesis by the preBötzinger complex.
doi:10.1523/jneurosci.2237-04.2005 pmid:15647488 fatcat:ptdmhxjpl5gephbsc6qzpvcg5e