Format

Send to

Choose Destination
FEBS Lett. 2014 Apr 17;588(8):1379-88. doi: 10.1016/j.febslet.2014.02.004. Epub 2014 Feb 15.

Differentiating connexin hemichannels and pannexin channels in cellular ATP release.

Author information

1
Department of Molecular Physiology and Biophysics, University of Virginia, Charlottesville, VA 22098, United States; Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, United States.
2
Department of Molecular Physiology and Biophysics, University of Virginia, Charlottesville, VA 22098, United States; Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908, United States. Electronic address: brant@virginia.edu.

Abstract

Adenosine triphosphate (ATP) plays a fundamental role in cellular communication, with its extracellular accumulation triggering purinergic signaling cascades in a diversity of cell types. While the roles for purinergic signaling in health and disease have been well established, identification and differentiation of the specific mechanisms controlling cellular ATP release is less well understood. Multiple mechanisms have been proposed to regulate ATP release with connexin (Cx) hemichannels and pannexin (Panx) channels receiving major focus. However, segregating the specific roles of Panxs and Cxs in ATP release in a plethora of physiological and pathological contexts has remained enigmatic. This multifaceted problem has arisen from the selectivity of pharmacological inhibitors for Panxs and Cxs, methodological differences in assessing Panx and Cx function and the potential compensation by other isoforms in gene silencing and genetic knockout models. Consequently, there remains a void in the current understanding of specific contributions of Panxs and Cxs in releasing ATP during homeostasis and disease. Differentiating the distinct signaling pathways that regulate these two channels will advance our current knowledge of cellular communication and aid in the development of novel rationally-designed drugs for modulation of Panx and Cx activity, respectively.

KEYWORDS:

ATP; Connexin hemichannel; Pannexin channel; Purinergic; Receptor

PMID:
24548565
PMCID:
PMC3996918
DOI:
10.1016/j.febslet.2014.02.004
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Wiley Icon for PubMed Central
Loading ...
Support Center