Skip to main content
  • Meeting abstract
  • Open access
  • Published:

Current-clamp experiments on primary hippocampal neurons shed light on the role of L-type voltage-gated calcium channels in depolarization shifts


Paroxysmal depolarization shifts are the cellular representations of interictal spikes. Interictal spikes (IIS) have a long history in the diagnosis of epilepsy. Previously, it was thought that IIS are largely asymptomatic, but there is growing evidence that beside being involved in epileptogenesis, they are also involved in the pathogenesis of various other neurological diseases. However, the pathomechanisms leading to the formation of IIS and how IIS may lead to functional neuronal impairment are poorly understood. In a previous study [1] we showed that L-type voltage-gated calcium channels (LTCCs) are capable of augmenting brief neuronal depolarizations. Hence, we were interested in the question whether LTCCs contribute to neuronal depolarization shifts (DS).


1 mM caffeine was applied as an epileptogenic agent, and LTCC activity was modulated by Bay K8644 (BayK) and isradipine, respectively.


In contrast to earlier studies on hippocampal slices [2], caffeine alone failed to induce DS in all but one out of 12 neurons tested. However, when BayK (3 µM) was co-administered, DS were readily evoked in about 60% of 21 neurons tested. DS were abolished by subsequent addition of isradipine (3 µM). Since oxidative stress has been shown to augment LTCC currents, we tested hydrogen peroxide in our DS assay, again employing caffeine co-administration. Within 5 min of exposure to 3 mM H2O2, DS appeared in a subpopulation of neurons. Testing both BayK and H2O2 on the same neurons we found that H2O2 evoked DS only in those neurons where BayK showed a clear DS-inducing effect. In those cells, where BayK failed to cause DS, H2O2 also had no effect.


Our data suggest that potentiation of LTCCs promotes the formation of depolarization shifts. Oxidative stress appears to be a pathogenic initiator of DS, and this activity may require LTCCs. Since LTCC augmentation is being considered as a pathological mechanism in neurodegenerative diseases, our data point to the possibility that the initiation of IIS may be a precipitating factor and that LTCC inhibition may provide a means to counteract neuropathogenic mechanisms.


  1. Geier P, Lagler M, Boehm S, Kubista H: Dynamic interplay of excitatory and inhibitory coupling modes of neuronal L-type calcium channels. Am J Physiol Cell Physiol. 2011, 300: C937-C949. 10.1152/ajpcell.00219.2010.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Moraidis I, Bingmann D, Lehmenkühler A, Speckmann EJ: Caffeine-induced epileptic discharges in CA3 neurons of hippocampal slices of the guinea pig. Neurosci Lett. 1991, 129: 51-54. 10.1016/0304-3940(91)90718-9.

    Article  CAS  PubMed  Google Scholar 

Download references


Supported by the Austrian Science Fund FWF (P19710 to H.K.).

Author information

Authors and Affiliations


Corresponding author

Correspondence to Helmut Kubista.

Rights and permissions

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reprints and permissions

About this article

Cite this article

Kubista, H., Rubi, L., Geier, P. et al. Current-clamp experiments on primary hippocampal neurons shed light on the role of L-type voltage-gated calcium channels in depolarization shifts. BMC Pharmacol 11 (Suppl 2), A28 (2011).

Download citation

  • Published:

  • DOI: