Inhibition of endoplasmic reticulum Ca²⁺ ATPase in preBötzinger complex of neonatal rat does not affect respiratory rhythm generation

Neuroscience. 2012 Nov 8;224:116-24. doi: 10.1016/j.neuroscience.2012.08.016. Epub 2012 Aug 18.

Abstract

PreBötzinger complex (preBötC) neurons in the brainstem underlie respiratory rhythm generation in vitro. As a result of network interactions, preBötC neurons burst synchronously to produce rhythmic premotor inspiratory activity. Each inspiratory neuron has a characteristic 10-20 mV, 0.3-0.8 s synchronous depolarization known as the inspiratory drive potential or inspiratory envelope, topped by action potentials (APs). Mechanisms involving Ca(2+) fluxes have been proposed to underlie the initiation of the inspiratory drive potential. An important source of intracellular Ca(2+) is the endoplasmic reticulum (ER) in which active Ca(2+) sequestration is mediated by a class of transporters termed sarco/endoplasmic reticulum Ca(2+) ATPases (SERCAs). We aim to test the hypothesis that disruption of Ca(2+) sequestration into the ER affects respiratory rhythm generation. We examined the effect of inhibiting SERCA on respiratory rhythm generation in an in vitro slice preparation. Bath application of the potent SERCA inhibitors thapsigargin or cyclopiazonic acid (CPA) for up to 90 min did not significantly affect the period or amplitude of respiratory-related motor output or integral and duration of inspiratory drive in preBötC neurons. We promoted the depletion of intracellular Ca(2+) stores by a transient bath application of 30 mM K(+) (high K(+)) in the continuous presence of thapsigargin or CPA. After washing out the high K(+), respiratory rhythm period and amplitude returned to baseline values. These results show that after inhibition of SERCA and depletion of intracellular Ca(2+) stores, respiratory rhythm remains substantially the same, suggesting that this source of Ca(2+) does not significantly contribute to rhythm generation in the preBötC in vitro.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Animals, Newborn
  • Brain Stem / physiology*
  • Calcium-Transporting ATPases / antagonists & inhibitors*
  • Endoplasmic Reticulum / metabolism*
  • Patch-Clamp Techniques
  • Rats
  • Respiration
  • Respiratory Mechanics / physiology*

Substances

  • Calcium-Transporting ATPases