1. On the Origin of Paroxysmal Depolarization Shifts: The Contribution of Cav1.x Channels as the Common Denominator of a Polymorphous Neuronal Discharge Pattern
- Author
-
Helmut Kubista, Karlheinz Hilber, Annika Kettner, Lena Rubi, Matej Hotka, Stefan Boehm, Xaver Koenig, Ulla Hochenegg, and Christiane Meyer
- Subjects
0301 basic medicine ,Voltage-gated ion channel ,Chemistry ,Paroxysmal depolarizing shift ,General Neuroscience ,food and beverages ,Depolarization ,Gating ,Hippocampal formation ,Epileptogenesis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Giant depolarizing potentials ,medicine ,Neuroscience ,Nucleus ,030217 neurology & neurosurgery - Abstract
Since their discovery in the 1960s, the term paroxysmal depolarization shift (PDS) has been applied to a wide variety of reinforced neuronal discharge patterns. Occurrence of PDS as cellular correlates of electrographic spikes during latent phases of insult-induced rodent epilepsy models and their resemblance to giant depolarizing potentials (GDPs) nourished the idea that PDS may be involved in epileptogenesis. Both GDPs and – in analogy – PDS may lead to progressive changes of neuronal properties by generation of pulsatile intracellular Ca2+ elevations. Herein, a key element is the gating of L-type voltage gated Ca2+ channels (LTCCs, Cav1.x family), which may convey Ca2+ signals to the nucleus. Accordingly, the present study investigates various insult-associated neuronal challenges for their propensities to trigger PDS in a LTCC-dependent manner. Our data demonstrate that diverse disturbances of neuronal function are variably suited to induce PDS-like events, and the contribution of LTCCs is essential to evoke PDS in rat hippocampal neurons that closely resemble GDPs. These PDS appear to be initiated in the dendritic sub-compartment. Their morphology critically depends on the position of recording electrodes and on their rate of occurrence. These results provide novel insight into induction mechanisms, origin, variability, and co-existence of PDS with other discharge patterns and thereby pave the way for future investigations regarding the role of PDS in epileptogenesis.
- Published
- 2021