Episodic respiratory motor output is decreased by 5‐HT3 receptor agonists and increased by 5‐HT3 receptor antagonists in isolated adult turtle brainstems

Abstract

Episodic breathing is a respiratory pattern marked by episodes of several consecutive breaths that are separated by non‐ventilatory pauses. Episodic breathing occurs naturally in some ectothermic vertebrates, but the underlying mechanisms are not known. Approximately 56% of isolated turtle brainstems produce single bursts of respiratory motor output on hypoglossal nerves (bursts/episode < 1.25), while 25% of isolated turtle brainstems produce episodic respiratory bursts (bursts/episode > 1.75; n=171; Johnson & Creighton, Am J Physiol Regul Integr Comp Physiol, 2005). Bath‐application of 5‐HT3 agonists, such as phenylbiguanide (PBG; 20 µM; n=8) or 1‐(m‐Chlorophenyl)biguanide hydrochloride (mCPBG; 50 µM; n=6), onto isolated turtle brainstems switched episodic respiratory bursts (2.04 ± 0.06 bursts/episode) into singlet bursts (1.31 ± 0.09 bursts/episode) after 1.0 h (P<0.001). Bath‐application of 5‐HT3 antagonists, such as tropisetron (50 µM; n=5) and MDL‐72222 (50 µM; n=3) tended to switch singlet respiratory bursts (1.05 ± 0.03 bursts/episode) into episodic bursts (1.52 ± 0.06 bursts/episode) after 2.0 h (P>0.05). These data suggest that 5‐HT3 receptors in the brainstem are involved in regulating episodic breathing in turtles.