Potential switch from eupnea to fictive gasping after blockade of glycine transmission and potassium channels.
This study evaluated possible neuronal mechanisms responsible for the transition from normal breathing (eupnea) to gasping. We hypothesized that a blockade of both inhibitory glycinergic synaptic transmission and potassium channels, combined with an increase in extracellular concentration of potassium, would induce a switch from an eupneic respiratory pattern to gasping. Efferent activities of the phrenic, vagal, and hypoglossal nerves were recorded during eupnea and ischemia-induced gasping in a perfused in situ preparation of the juvenile rat (4-6 wk of age). To block potassium channels, 4-aminopyridine (4-AP, 1-10 microM) was administered. Strychnine (0.2-0.6 microM) was used to block glycinergic neurotransmission. After administrations of 4-AP, excess extracellular potassium (10.25-17.25 mM), and strychnine, the incrementing pattern of eupneic phrenic activity was altered to a decrementing discharge. Hypoglossal and vagal activities became concentrated to the period of the phrenic burst with expiratory activity being reduced or eliminated. These changes in neural activities were similar to those in ischemia-induced gasping. Results are consistent with the concept that the elicitation of gasping represents a switch from a network-based rhythmogenesis for eupnea to a pacemaker-driven mechanism.
St -John
Walter M
WM
Department of Physiology, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA.
Rybak
Ilya A
IA
Paton
Julian F R
JF
D015761:4-Aminopyridine / Q000494:pharmacology; D000367:Age Factors; D000818:Animals; D001917:Brachial Plexus / Q000502:physiology; D001933:Brain Stem / Q000502:physiology; D005998:Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018684:Glycine Agents / Q000494:pharmacology; D007002:Hypoglossal Nerve / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D010791:Phrenic Nerve / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014630:Vagus Nerve / Q000502:physiology
D018684:Glycine Agents; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011189:Potassium Chloride; D015761:4-Aminopyridine; D013331:Strychnine; D005998:Glycine