Effects on ventilation (VE) and neuromodulator concentration of cholinergic receptor blockade at the pre‐Bötzinger Complex (preBötC)

Abstract

We previously found that microdialysis of the muscarinic acetylcholine receptor antagonist, Atropine (AT, 50mM) in mock cerebrospinal fluid (mCSF) into the Kӧlliker‐Fuse Nucleus (KFN) of awake and sleeping goats (n=6) reduces VE and breathing frequency (f) (J Appl Physiol, 109: 159–170, 2010). In contrast, dialysis of 50mM AT into the preBötC of awake goats (n=6) increased VE and f, and increased the concentration of serotonin (5‐HT) and substance P (SP) in the effluent mCSF (FASEB J, 25: 1074.1, 2011). To gain insight into the mechanism by which cholinergic receptor blockade in the preBötC increases VE and f, we dialyzed in one awake goat, mCSF into the preBötC on one side, and simultaneously dialyzed 5mM or 50mM AT into the preBötC of the contralateral side. 5mM AT did not affect VE, f, or effluent 5‐HT, but minimally increased effluent SP, indicating a dose‐dependent AT effect. In contrast, 50mM AT increased VE, f, and effluent 5‐HT and SP. The increase in 5‐HT and SP was restricted to the side receiving AT. These data suggest that cholinergic receptor blockade in the preBötC affects local, not global, levels of these excitatory neuromodulators, which affect the level of breathing. We hypothesize that AT blocks cholinergic receptors of pre‐synaptic 5‐HT and SP terminals at the preBötC, the effect of which is enhanced release of 5‐HT and SP, which subsequently increases VE and f. Support: NIH HL25739 & Veterans Administration