MODULATION OF MECHANICALLY INDUCED CALCIUM WAVES IN HIPPOCAMPAL ASTROGLIAL CELLS - INHIBITORY EFFECTS OF ALPHA(1)-ADRENERGIC STIMULATION

The effects of different adrenoceptor agonists were investigated on me chanically induced Ca2+ waves in astroglial cells in astroglial-neuron al mixed cultures from rat hippocampus. In the initial part of the stu dy some properties of the waves were characterized. The results show t hat the initiation of the Ca2+ waves was not critically dependent on e xtracellular Ca2+ but both the calcium signal and the propagation area of the calcium wave were significantly reduced when the experiments w ere performed in Ca2+-free buffer. In addition, using the phospholipas e C (PLC) inhibitor U-73122 (1 mu M) and the gap junction uncoupler oc tanol (1 mM), the results showed that the Ca2+ wave propagation requir ed PLC activation and functional gap junctions. Further, the data also showed that the protein kinase C (PKC) activator phorbol-12-myristate -13-acetate (PMA 150 nM) reduced the spreading of the waves. The adren oceptor agonists isoproterenol (iso; beta), phenylephrine (phe; alpha( 1)) and clonidine(clon; alpha(2)) were evaluated for their short-term (< 30 s) effects on the wave propagation. The propagation area was per sistently decreased 1, 3 and 5 min after removal of phe. No effects we re observed after incubation with iso or cion. Furthermore, using U-73 122 or PMA together with phe, shortly incubated, the experiments showe d that PLC was a central regulator in the initial phase of the initiat ion procedure of wave propagation. However, under these conditions PKC was shown not to be involved. Instead it appeared that PKC exerted it s inhibitory action on the Ca2+ waves in a latter phase, after prolong ed phe exposure. Taken together, the results show that the propagation of Ca2+ waves between astroglial cells in primary cultures can be inh ibited/regulated in two principally different ways which involve a pro nounced time component. The results also further point out the adrener gic signaling system as an important mediator of dynamic neuron-astrog lial information exchange. (C) 1998 Elsevier Science B.V. All rights r eserved.