Potassium-dependent calcium influx in acutely isolated hippocampal astrocytes

Potassium depolarization can increase the intracellular ionized calcium concentration ([Ca 2+] i) of cultured astrocytes, but it is not known if astrocytes that have matured in the intact CNS also exhibit voltage-dependent [Ca 2+] i signalling. To address this issue, fluorometric measurements of [Ca 2+] i were obtained from astrocytes acutely isolated from young adult rat hippocampus. In control artificial cerebrospinal fluid containing 5 mM [K +] o, average resting [Ca 2+] i was 195 nM. Elevation of [K +] o to 50 mM caused [Ca 2+] i to increase 150 nM to 1 μM above resting levels. The threshold [K +] o necessary to evoke an elevation in [Ca 2+] i was 20–25 mM, and the magnitude of the [Ca 2+] i signal grew progressively with increasing [K +] o (up to 50 mM). These [Ca 2+] i increases were blocked completely by removal of external Ca 2+, and markedly suppressed by the calcium channel blockers verapamil (30 μM and greater) and Co 2+ (1 mM). Neither reversal of Na +-Ca 2+ exchange, nor Ca 2+-activated Ca 2+ release, nor Ca 2+ influx through stretch-activated channels contributed to the [Ca 2+] i increase. These results suggest that [K +] o-evoked [Ca 2+] i signals are mediated by influx through voltage-gated calcium channels. In contrast to results from cultured astrocytes and acutely isolated neurons, these [Ca 2+] i increases were insensitive to dihydropyridine compounds. We conclude that increases in interstitial [K +], observed in situ during several pathological conditions, trigger voltage-dependent [Ca 2+] i signals in astroglial cells. This may constitute an important form of neuron-to-glial communication.