Extracellular pH modulates aluminium-blockade of mammalian voltage-activated calcium channel currents.
The pH-dependence of aluminium (Al) blockade of voltage activated calcium channels (VACCs) was investigated. Using cultures of rat dorsal root ganglion (DRG) neurones, whole-cell patch-clamp experiments were performed. Various concentrations of Al were extracellularly applied within solutions of different pH-values. The block of VACC currents was highly pH-dependent. At pH 7.3-7.8, the concentration-response curve shifted slightly to higher concentrations, whereas at pH 6.4-6.9 a pronounced shift to lower concentrations was observed. This effect could be due to changes of the chemical equilibria of the different Al species or to altered properties of the VACCs. Thus, pH-shifts may influence the interactions of Al with VACCs making them more susceptible to the effects of Al and therefore contribute to its toxicity.
Platt
B
B
Heinrich Heine Universität, Düsseldorf, Germany.
Haas
H
H
Büsselberg
D
D
D000535:Aluminum / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D004594:Electrophysiology; D005110:Extracellular Space / Q000187:drug effects / Q000502:physiology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D000535:Aluminum