title: Substitution of extracellular Ca2+ by Sr2+ prolongs inspiratory burst in pre-Bötzinger complex inspiratory neurons.
abstract: The pre-Bötzinger complex (preBötC) underlies inspiratory rhythm generation. As a result of network interactions, preBötC neurons burst synchronously to produce rhythmic premotor inspiratory activity. Each inspiratory burst consists of action potentials (APs) on top of a 10- to 20-mV synchronous depolarization lasting 0.3-0.8 s known as inspiratory drive potential. The mechanisms underlying the initiation and termination of the inspiratory burst are unclear, and the role of Ca(2+) is a matter of intense debate. To investigate the role of extracellular Ca(2+) in inspiratory burst initiation and termination, we substituted extracellular Ca(2+) with Sr(2+). We found for the first time an ionic manipulation that significantly interferes with burst termination. In a rhythmically active slice, we current-clamped preBötC neurons (Vm ≅ -60 mV) while recording integrated hypoglossal nerve (∫XIIn) activity as motor output. Substitution of extracellular Ca(2+) with either 1.5 or 2.5 mM Sr(2+) significantly prolonged the duration of inspiratory bursts from 653.4 ± 30.7 ms in control conditions to 981.6 ± 78.5 ms in 1.5 mM Sr(2+) and 2,048.2 ± 448.5 ms in 2.5 mM Sr(2+), with a concomitant increase in decay time and area. Substitution of extracellular Ca(2+) by Sr(2+) is a well-established method to desynchronize neurotransmitter release. Our findings suggest that the increase in inspiratory burst duration is determined by a presynaptic mechanism involving desynchronization of glutamate release within the network.
authors.affiliation: Centro de Investigaciones Cerebrales, Dirección General de Investigaciones, Universidad Veracruzana, Xalapa, Veracruz, Mexico; and comorgado@uv.mx.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Morgado-Valle
authors.affiliation: Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico.
authors.forename: Juan
authors.initials: J
authors.lastname: Fernandez-Ruiz
authors.affiliation: Centro de Investigaciones Cerebrales, Dirección General de Investigaciones, Universidad Veracruzana, Xalapa, Veracruz, Mexico; and.
authors.forename: Leonor
authors.initials: L
authors.lastname: Lopez-Meraz
authors.affiliation: Centro de Investigaciones Cerebrales, Dirección General de Investigaciones, Universidad Veracruzana, Xalapa, Veracruz, Mexico; and.
authors.forename: Luis
authors.initials: L
authors.lastname: Beltran-Parrazal
mesh_terms: D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D007002:Hypoglossal Nerve / Q000187:drug effects / Q000502:physiology; D001239:Inhalation; D007395:Interneurons / Q000187:drug effects* / Q000502:physiology; D008526:Medulla Oblongata / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D051381:Rats; D013324:Strontium / Q000494:pharmacology*
chemical_list: D002118:Calcium; D013324:Strontium
keywords: breathing; burst termination; respiratory pattern; respiratory rhythm generation; strontium