TY - JOUR T1 - Predictions and experimental tests of a new biophysical model of the mammalian respiratory oscillator JF - bioRxiv DO - 10.1101/2021.10.29.466442 SP - 2021.10.29.466442 AU - Ryan S. Phillips AU - Hidehiko Koizumi AU - Yaroslav I. Molkov AU - Jonathan E. Rubin AU - Jeffrey C. Smith Y1 - 2021/01/01 UR - http://biorxiv.org/content/early/2021/11/01/2021.10.29.466442.abstract N2 - Previously our computational modeling studies (Phillips et al., 2019) proposed that neuronal persistent sodium current (INaP) and calcium-activated non-selective cation current (ICAN) are key biophysical factors that, respectively, generate inspiratory rhythm and burst pattern in the mammalian preBötzinger complex (preBötC) respiratory oscillator. Here, we experimentally tested and confirmed three predictions of the model from new simulations concerning the roles of INaP and ICAN: (1) INaP and ICAN blockade have opposite effects on the relationship between network excitability and preBötC rhythmic activity; (2) INaP is essential for preBötC rhythmogenesis; (3) ICAN is essential for generating the amplitude of rhythmic output but not rhythm generation. These predictions were confirmed via optogenetic manipulations of preBötC network excitability during graded INaP or ICAN blockade by pharmacological manipulations in neonatal mouse slices in vitro. Our results support and advance the hypothesis that INaP and ICAN mechanistically underlie rhythm and inspiratory burst pattern generation, respectively, in the isolated preBötC.Competing Interest StatementThe authors have declared no competing interest. ER -