Hypertonicity-induced cation channels.
Whenever studied in a quantitative fashion, hypertonicity-induced cation channels (HICCs) are found to be the main mediators of regulatory volume increase. In most instances, these channels are either inhibited by amiloride (but insensitive to Gd3+ and flufenamate) or they are efficiently blocked by Gd3+ and flufenamate (but insensitive to amiloride). Of note, however, from two preparations so far a mixed type of pharmacology has also been reported. Whereas the ion selectivity of amiloride-sensitive HICCs has not been studied in much detail yet, amiloride-insensitive channels are either equally permeable to Na+, K+, Cs+ and Li+ but impermeable to N-methyl-D-glucamine (NMDG+) or they exhibit a permeability to Li+ and NMDG+ that amounts to some 50% when compared with that of Na+. Also in this respect, however, some peculiarities do exist. Concerning the actual molecular correlate, evidence was reported that HICCs may be related to the (amiloride-sensitive) epithelial Na+ channel and/or to transient receptor potential channels. Recent findings suggest that HICCs may contribute to cell proliferation, just as the K+ channels that are employed in regulatory volume decrease are mediators of the opposing process, i.e. apoptosis.
Wehner
F
F
Max-Planck-Institut für molekulare Physiologie, Dortmund, Germany.
Bondarava
M
M
ter Veld
F
F
Endl
E
E
Nürnberger
H R
HR
Li
T
T
D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D002412:Cations; D002462:Cell Membrane / Q000187:drug effects; D002463:Cell Membrane Permeability; D048429:Cell Size; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006982:Hypertonic Solutions / Q000378:metabolism; D009994:Osmolar Concentration; D015221:Potassium Channels / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology*
D002412:Cations; D006982:Hypertonic Solutions; D015221:Potassium Channels; D026941:Sodium Channel Blockers; D000584:Amiloride