Role of gap junctions in CO₂ chemoreception and respiratory control

Abstract

Gap junctions are composed of connexins, which are organized into intercellular channels that form transmembrane pathways between neurons (cell-cell coupling), and in some cases, neurons and glia, for exchange of ions and small molecules (metabolic coupling) and ionic current (electrical coupling). Cell-cell coupling via gap junctions has been identified in brain stem neurons that function in CO2/H+ chemoreception and respiratory rhythmogenesis; however, the exact roles of gap junctions in respiratory control are undetermined. Here we review the methods commonly used to study gap junctions in the mammalian brain stem under in vitro and in vivo conditions and briefly summarize the anatomical, pharmacological, and electrophysiological evidence to date supporting roles for cell-cell coupling in respiratory rhythmogenesis and central chemoreception. Specific research questions related to the role of gap junctions in respiratory control are suggested for future research.

Hypercapnia modulates synaptic interaction of cultured brainstem neurons

“…Electrical couplings have been previously shown in brainstem neurons from neonatal rats (Huang et al 1997;Solomon and Dean 2002;Dean et al 2002), which is supported by our current studies in cultured brainstem neurons. There are several connexin proteins including connexins 26, 32 and 36 expressed in brainstem neurons, they form gap junction between neurons and coupled electrical and chemical activity between cells (Condorelli et al 2000;Solomon et al 2001;Solomon 2003).…”

“…4C 1 , D 1 ) (Gustafsson and Jankowska 1976;Jiang and Lipski 1990). When they were plotted in coupling efficiency against peak-mean ratio, these large central peaks were clearly segregated from the common inputs and pericentral peaks shown above (Fig 5), suggesting that these action potentials were recorded from two neurons with electrical synapses or gap junctions as have been previously observed in brainstem neurons (Huang et al 1997;Solomon and Dean 2002;Dean et al 2002). Consistently, the coupling efficiency, i.e., peak spike counts of the target unit divided by spiked counts of the reference unit, was almost completely suppressed in the presence of 2 mM halothane, a gap junction blocker (Fig.…”

An Analysis between Pre- and Post-exercise of the Respiratory and Metabolic State for the Acute and Subacute Stroke Patients

“…Whole animal and in vitro studies indicate that ventral and dorsal respiratory group on medulla oblongata and pneumotaxic center on pons regulate respiration according concentrations on chemoreceptors of CO 2 and hydrogen ions, those are distributed throughout the brainstem [14]. Peripheral chemoreceptor system is also involved in respiration by detecting lack of O 2 on carotid and aortic bodies, then it makes respiration center in brain excited [15].…”

Ventilatory effects of gap junction blockade in the RTN in awake rats

“…The function of gap junctions in developing animals may be to amplify inputs and enhance the formation of local circuits that will ultimately depend on chemical synaptic transmission (68). The low resistance electrical pathway provided by gap junctions may also synchronize activity among cells and synchronization of multiple cells may coordinate and amplify responses to particular stimuli (7,12,14,42).…”

“…Of the respiratory-related sites in which gap junctions are expressed, the pre-Bötzinger complex, locus ceruleus (LC), retrotrapezoid nucleus (RTN) in the ventrolateral medulla, and nucleus of the solitary tract (NTS) are sensitive to CO 2 (9,44,63). Therefore, gap junctions may be a necessary component of central CO 2 chemosensitivity (12). However, virtually all of the electrophysiological work implicating gap junctions in central CO 2 chemosensitivity had been performed in brain stem preparations from neonatal animals, and there has been little or no evidence that gap junctions played a role in respiratory control in older animals.…”