| 11013130 |
Kondo RP, Wang SY, John SA, Weiss JN, Goldhaber JI: Metabolic inhibition activates a non-selective current through connexin hemichannels in isolated ventricular myocytes. J Mol Cell Cardiol. 2000 Oct;32(10):1859-72.
Intracellular Na (+) accumulation and K (+) loss play important roles in the pathogenesis of arrhythmias and injury in the ischemic heart. We investigated the role of metabolically sensitive connexin hemichannels as a potential route for Na (+) influx and K (+) efflux during ischemia, using dye uptake and electrophysiological measurements to assay hemichannel activity in isolated rabbit ventricular myocytes. Consistent with the known size selectivity of connexin hemichannels,;50% of myocytes exposed to either low extracellular Ca (2+)(an established method for opening connexin hemichannels) or to metabolic inhibitors (a recently described method for opening hemichannels) accumulated fluorescent dyes with <1000 MW (propidium iodide and calcein), but excluded a larger dye with 1500-3000 MW (dextran-rhodamine). Using the whole cell patch clamp technique, we found that metabolic inhibitors activated a non-selective current permeant to both small and large cations, and blocked by La (3+), similar to the properties of connexin 43 when overexpressed in human embryonic kidney (HEK) cells. These findings indicate that isolated cardiac myocytes endogenously express metabolically-sensitive connexin hemichannels. If activated during ischemia, these hemichannels could contribute significantly to altered ionic fluxes promoting arrhythmias and myocardial injury. |
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