Ryanodine receptor/Ca(2+) release mechanisms in rhythmically active respiratory neurons of cats in vivo.

The cytosolic Ca(2+) released from internal stores is important for distinctive cell functions. To assess the role of ryanodine/Ca(2+) releasing mechanisms in the rhythmic activity of respiratory neurons, effects of intracellular injection of ryanodine on the membrane potential trajectory of postinspiratory and augmenting inspiratory neurons were investigated in unanesthetized, decerebrate, paralyzed and artificially ventilated cats. Ryanodine injection hyperpolarized the membrane and decreased input resistance throughout the respiratory cycle in both types of respiratory neurons. Specifically, membrane repolarization during postinspiration was accelerated in postinspiratory neurons, and the large hyperpolarization at the onset of postinspiration was increased in augmenting inspiratory neurons. Spike-afterhyperpolarization consisting of a fast, early component and slow, late component increased in size after ryanodine, resulting in prolongation of inter-spike intervals and decrease of burst discharge. Intracellular injection of caffeine produced similar effects on these respiratory neurons, and Ruthenium Red, an antagonist of ryanodine receptors, had opposite effects. Immunoreactivity for ryanodine receptors was detected in all respiratory neurons labeled intracellularly with neurobiotin. These results demonstrate that ryanodine-sensitive Ca(2+) stores modulate the periodic membrane potential fluctuations and spike activity in respiratory neurons.