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In conclusion, Cx and Panx hemichannels form an important pathway for release
of ATP. This release contributes to IC in addition to the well-known gap junc-
tional IC. Thus, hemichannels may contribute to bystander and/or good samaritan
effects in pathological conditions, even between cells that are disjointed and lack gap
junctionial coupling. Further research is needed to investigate factors that regulate
the open probability of hemichannels and the role of hemichannels in physiolog-
ical and pathological conditions in different cell types. A clear distinction should
be made between effects that can be attributed to the Cx or Panx hemichannel-
mediated IC versus effects of gap junctional IC or effects due to expression and
distribution of these proteins in intracellular compartments, such as mitochondria
or endoplasmic reticulum. Availability of Panx and Cx isoform-specific agonists
and antagonists, and specific hemichannel blockers, in addition to gene abblation,
silencing, mutation and protein expression studies, would be very helpful to clarify
the role of the hemichannels in physiological and pathological conditions in dif-
ferent cell types and may provide therapeutic tools for treatment of pathological
conditions associated with abberant IC.
Acknowledgments
Supported by FWO-Vlaanderen G.0218.03, GOA/2004/07, IAP program
5/05 (BH and JV) and NIH grant R21-EY019119 and Faculty Research Grant, VP of Research, IU
Bloomington, IN (SPS).
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