Selective absence of calcium spikes in Purkinje cells of staggerer mutant mice in cerebellar slices maintained in vitro.

The bioelectrical properties of Purkinje cells (intrasomatic recordings) were studied in sagittal cerebellar slices of both adult staggerer and control mice. Mean input resistances of Purkinje cells were 25 +/- 4 M omega and 48 +/- 7 M omega in normal and staggerer mice respectively. In both groups, time-dependent inward rectifications were apparent in the hyperpolarizing voltage-responses. In normal mice, tetrodotoxin (TTX)-sensitive simple spikes and slower-rising multiphasic spikes, abolished when Ca was replaced by Cd in the bath, spontaneously occurred in Purkinje cells. These Na- and Ca-dependent spikes were also elicited by depolarizing current pulses. In the mutant, Ca spikes were never observed, even in strongly depolarized cells. On the contrary, TTX-sensitive simple spikes occurred spontaneously or were elicited by depolarizing current pulses. When Ca was replaced by Ba in the bath, the Ca spikes evoked in normal Purkinje cells by direct stimulation were first enhanced and then replaced by prolonged action potentials (1-6 s in duration) which were TTX-resistant and Cd-sensitive. These (Ba) action potentials were also triggered by climbing fibre activation of the cells. In staggerer mice, Ca spikes were never elicited by direct stimulation in Ba-containing medium, although in a few cells prolonged action potentials were occasionally elicited by depolarizing current pulses. However, this latter type of response was never evoked by climbing fibre activation of Purkinje cells. In the mutant, extracellular application of tetraethylammonium (TEA) generated prolonged action potentials, the plateaux of depolarization of which were less positive than those elicited by Ba in control mice. These plateaux were abolished by TTX and left unaffected by the substitution of Ca by Cd in the bath, suggesting that they were due to a non-inactivating Na conductance. On the whole, the present study strongly suggests that voltage-dependent Ca channels are missing in most staggerer Purkinje cells or at least that their characteristics and/or distribution are such that they cannot be activated. Na channels appear unaffected.