Ca2+ permeability of the sustained proton-induced cation current in adult rat dorsal root ganglion neurons.
1. Microfluorometric Ca2+ measurements using FURA-2 and whole cell patch-clamp recordings were performed to investigate the Ca2+ permeability of ion channels underlying the proton-induced sustained cation current in adult rat dorsal root ganglion neurons. 2. In a subpopulation of these neurons, extracellular application of acidic solutions (pH 5.1) elicited a sustained cation current and a concomitant reversible rise in the intracellular free Ca2+ concentration ([Ca2+]i), which depended on the presence of external Ca2+. Ruthenium red (10 microM) reduced both the current and the rise in [Ca2+]i to about the same extent. 3. In the presence of 2 mM external Ca2+, sustained proton-induced currents reversed sign at -4.6 +/- 1.2 (SE) mV, with external Na+ and internal Cs+ as the major charge carriers. Increasing the external Ca2+ concentration to 30 mM shifted the reversal potential (Erev) by 3.0 +/- 0.9 mV toward more positive values, suggesting a permeability ratio of Ca2+/Cs+ of 0.41. A similar value (0.35) could be obtained from Erev (-21 mV) under bi-ionic conditions with 100 mM external Ca2+ and 154 mM internal Cs+. 4. These results demonstrate that the proton-activated cation channels investigated here are moderately permeable to Ca2+. This may lead to pathophysiologically relevant increases in [Ca2+]i on prolonged exposure of the cells to an acidic environment in inflamed or ischemic tissue.
Zeilhofer
H U
HU
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität Erlangen-Nürnberg, Germany.
Swandulla
D
D
Reeh
P W
PW
Kress
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002412:Cations / Q000378:metabolism*; D002478:Cells, Cultured / Q000378:metabolism; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism*; D017136:Ion Transport / Q000502:physiology*; D011522:Protons; D051381:Rats; D017208:Rats, Wistar
D002412:Cations; D011522:Protons; D002118:Calcium