Substitution of extracellular Ca2+ by Sr2+ prolongs inspiratory burst in pre-Botzinger complex inspiratory neurons

作者：Morgado Valle Consuelo^*; Fernandez Ruiz Juan; Lopez Meraz Leonor; Beltran Parrazal Luis

来源：Journal of Neurophysiology, 2015, 113(4): 1175-1183.

DOI：10.1152/jn.00705.2014

• respiratory rhythm generation
• breathing
• strontium
• respiratory pattern
• burst termination

The pre-Botzinger complex (preBotC) underlies inspiratory rhythm generation. As a result of network interactions, preBotC 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 Ca2+ is a matter of intense debate. To investigate the role of extracellular Ca2+ in inspiratory burst initiation and termination, we substituted extracellular Ca2+ with Sr2+. We found for the first time an ionic manipulation that significantly interferes with burst termination. In a rhythmically active slice, we current-clamped preBotC neurons(V-m congruent to -60 mV) while recording integrated hypoglossal nerve (integral XIIn) activity as motor output. Substitution of extracellular Ca2+ with either 1.5 or 2.5 mM Sr2+ significantly prolonged the duration of inspiratory bursts from 653.4 +/- 30.7 ins in control conditions to 981.6 +/- 78.5 ins in 1.5 mM Sr2+ and 2,048.2 +/- 448.5 ms in 2.5 MM. Sr2+, with a concomitant increase in decay time and area Substitution of extracellular Ca2+ by Sr2+ 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.

• 出版日期2015-2-15