Ca^<2+> and signal transduction in CNS neurones.

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The functional roles of Ca^<2+> in central neurones were clarified, using nystatin-perforated patch-recording configuration applied to acutely dissociated neurones of the rats. 1. Influx of Ca^<2+> through Iigand-gated ion channels : In the neurons of the nucleus tractus solitarii (NTS) and Meynert nucleus, ATP and kainate were shown to activate large cationic current and the subsequent Ca^<2+>-dependent K^+ current (I_<K(Ca)>) by way of Ca^<2+> that directly came though the large cation channel. The large cationic current of the Meynert neurones in response to NMDA was diminished as the age of the animals increased, whereas that to kainate was potentiated. Ca^<2+> permeability of NMDA was constant during development, while that of kainate was decreased. Kainate-induced I_<K(Ca)> was more pronounced in the aged rats. 2. Influx of Ca^<2+> through voltage-dependent Ca^<2+> channels (VDCCs) : By using specific toxins, the five subtypes of VDCC (L,N,P,Q,R) were shown to be distributed differentially in different regions of the CNS.Somatostatin suppressed N-type VDCC in CA1 pyramidal neurones, whereas noradrenaline suppressed N-, P- and Q-types in NTS neurones. The VDCC responsible for synaptic transmission in Meynert 'synaptic bouton' preparation was L- and P-types, with the L-type showing different properties to those of somatic one. 3. Release of Ca^<2+> from intracellular Ca^<2+> store : The agonists of metabotropic glutamate receptors, muscarinic acetylcholine receptors and thyrotropin-releasing hormone receptor activated I_<K(Ca)> in CA1 pyramidal neurones by way of G protein * phospholipase C * IP_3 * Ca^<2+> release from IP_3-sensitive Ca^<2+> store * I_<K(Ca)>. These results indicate that Ca^<2+> serves as a negative feedback mechanism by activating I_<K(Ca)> and that the mechanism is well developed in aged rats. It is further suggested that VDCCs in CNS manifest region- and subtype-specific properties.