Calcium channels in excitable membranes are essential for many cellular functions. Recent analyses of the burst-firing mode of some vertebrate neurones suggest that changes in their functional state are controlled by a Ca conductance that is largely inactivated at resting membrane potentials (-50 to -60 mV), but becomes activated following a conditioning hyperpolarization of the cell membrane. Here, using chick and rat sensory neurones, we present evidence for a new type of Ca channel with time- and voltage-dependent properties which is probably responsible for the inactivation behaviour of the Ca conductance. At membrane potentials between -50 and +10 mV, openings of this channel last 3-6 ms and tend to occur in rapid succession. Inactivation of this channel is indicated by prolonged and eventually complete closures brought about by long-lasting depolarizing voltage steps. This channel coexists in isolated membrane patches with the more common Ca channel which is less sensitive to changes in holding potential and shows a considerably shorter average life time and smaller currents.

Extracellular calcium and potassium activities (aCa and aK) as well as neuronal activity were simultaneously recorded with ion-sensitive electrodes in the somatosensory cortex of cats. Baseline aCa was 1.2-1.5 mM/l, baseline aK 2.7-3.2 mM/l. Transient decreases in aCa and simultaneous increases in aK were evoked by repetitive stimulation of the contralateral forepaw, the nucleus ventroposterolateralis thalami and the cortical surface. Considerable decreases in aCa (by up to 0.7 mM/l) were found during seizure activity. A fall in aCa preceded the onset of paroxysmal discharges and the rise in aK after injection of pentylene tetrazol. The decrease in aCa led also the rise in aK during cyclical spike driving in a penicillin focus. It is concluded that alterations of Ca++ dependent mechanisms participate in the generation of epileptic activity.

The time course of local changes of the extracellular space (ES) was investigated by measuring concentration changes of repeatedly injected tetramethylammonium (TMA+) and choline (Ch+) ions for which cell membranes are largely impermeable. After stimulus-induced extracellular [K+] elevations the delta [TMA+] and delta [Ch+] signals recorded with nominally K+-selective liquid ion-exchanger microelectrodes increased by up to 100%, thus indicating a reduction of the ES down to one half of its initial size. The shrinkage was maximal at sites where the K+ release into the ES was also largest. At very superficial and deep layers, however, considerable increases in extracellular K+ concentration were not accompanied by significant reductions in the ES. These findings can be explained as a consequence of K+ movement through spatially extended cell structures. Calculations based on a model combining the spatial buffer mechanism of Kuffler and Nicholls (1966) to osmolarity changes caused by selective K+ transport through primarily K+ permeable membranes support this concept. Following stimulation additional iontophoretically induced [K+]0 rises were reduced in amplitude by up to 35%, even at sites where maximal decreases of the ES were observed. This emphasizes the importance of active uptake for K+ clearance out of the ES.

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The effects of noradrenaline and dopamine on voltage-dependent Ca currents were investigated in cultured dorsal root and sympathetic ganglion neurons from chick embryos. At concentrations of 1 to 10 microM, bath application of the neurotransmitters caused a general depression of inward Ca currents. Above -20 mV the decrease of the current amplitude was reversible and accompanied by a 2-10-fold prolongation of the activation time course. Below -20 mV, where a low voltage-activated Ca component is turned on, the size of the currents was reduced by 40% with little effect on the time course. Despite extensive wash-out, little sign of reversibility was observed in this case. Single-channel current recording in outside-out membrane patches revealed that at low membrane potentials dopamine and noradrenaline reversibly reduced single Ca-channel activity. This finding supports the view that in sensory and sympathetic neurons, both neurotransmitters affect the membrane conductance by modulating Ca permeability and not by activating catecholamine-specific channels able to carry transient outward currents. The probability of Ca channel opening is strongly reduced by addition of 10 microM of either catecholamine to the bath. The possible involvement of a voltage-dependent block of Ca channels by the neurotransmitters is discussed.