Potassium-dependent calcium influx in acutely isolated hippocampal astrocytes.
Potassium depolarization can increase the intracellular ionized calcium concentration ([Ca2+]i) of cultured astrocytes, but it is not known if astrocytes that have matured in the intact CNS also exhibit voltage-dependent [Ca2+]i signalling. To address this issue, fluorometric measurements of [Ca2+]i were obtained from astrocytes acutely isolated from young adult rat hippocampus. In control artificial cerebrospinal fluid containing 5 mM [K+]o, average resting [Ca2+]i was 195 nM. Elevation of [K+]o to 50 mM caused [Ca2+]i to increase 150 nM to 1 microM above resting levels. The threshold [K+]o necessary to evoke an elevation in [Ca2+]i was 20-25 mM, and the magnitude of the [Ca2+]i signal grew progressively with increasing [K+]o (up to 50 mM). These [Ca2+]i increases were blocked completely by removal of external Ca2+, and markedly suppressed by the calcium channel blockers verapamil (30 microM and greater) and Co2+ (1 mM). Neither reversal of Na(+)-Ca2+ exchange, nor Ca(2+)-activated Ca2+ release, nor Ca2+ influx through stretch-activated channels contributed to the [Ca2+]i increase. These results suggest that [K+]o-evoked [Ca2+]i signals are mediated by influx through voltage-gated calcium channels. In contrast to results from cultured astrocytes and acutely isolated neurons, these [Ca2+]i increases were insensitive to dihydropyridine compounds. We conclude that increases in interstitial [K+], observed in situ during several pathological conditions, trigger voltage-dependent [Ca2+]i signals in astroglial cells. This may constitute an important form of neuron-to-glial communication.
Department of Neuroscience, University of Calgary, Alberta, Canada.
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Duffy
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MacVicar
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D003592:Cytophotometry; D004095:Dihydropyridines / Q000494:pharmacology; D005456:Fluorescent Dyes; D016257:Fura-2; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D007211:Indoles; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger; D013347:Subcellular Fractions / Q000378:metabolism
D015220:Calcium Channels; D002352:Carrier Proteins; D004095:Dihydropyridines; D005456:Fluorescent Dyes; D007211:Indoles; D011725:Pyridines; D019831:Sodium-Calcium Exchanger; D003994:Bucladesine; D012964:Sodium; C048960:indo-1; D011188:Potassium; D002118:Calcium; D016257:Fura-2