Control of the propagation of dendritic low-threshold Ca(2+) spikes in Purkinje cells from rat cerebellar slice cultures

J Physiol. 2002 Apr 1;540(Pt 1):57-72. doi: 10.1113/jphysiol.2001.013294.

Abstract

To investigate the ionic mechanisms controlling the dendrosomatic propagation of low-threshold Ca(2+) spikes (LTS) in Purkinje cells (PCs), somatically evoked discharges of action potentials (APs) were recorded under current-clamp conditions. The whole-cell configuration of the patch-clamp method was used in PCs from rat cerebellar slice cultures. Full blockade of the P/Q-type Ca(2+) current revealed slow but transient depolarizations associated with bursts of fast Na(+) APs. These can occur as a single isolated event at the onset of current injection, or repetitively (i.e. a slow complex burst). The initial transient depolarization was identified as an LTS Blockade of P/Q-type Ca(2+) channels increased the likelihood of recording Ca(2+) spikes at the soma by promoting dendrosomatic propagation. Slow rhythmic depolarizations shared several properties with the LTS (kinetics, activation/inactivation, calcium dependency and dendritic origin), suggesting that they correspond to repetitively activated dendritic LTS, which reach the soma when P/Q channels are blocked. Somatic LTS and slow complex burst activity were also induced by K(+) channel blockers such as TEA (2.5 x 10(-4) M) charybdotoxin (CTX, 10(-5) M), rIberiotoxin (10(-7) M), and 4-aminopyridine (4-AP, 10(-3) M), but not by apamin (10(-4) M). In the presence of 4-AP, slow complex burst activity occurred even at hyperpolarized potentials (-80 mV). In conclusion, we suggest that the propagation of dendritic LTS is controlled directly by 4-AP-sensitive K(+) channels, and indirectly modulated by activation of calcium-activated K(+) (BK) channels via P/Q-mediated Ca(2+) entry. The slow complex burst resembles strikingly the complex spike elicited by climbing fibre stimulation, and we therefore propose, as a hypothesis, that dendrosomatic propagation of the LTS could underlie the complex spike.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / pharmacology
  • Action Potentials / drug effects
  • Action Potentials / physiology*
  • Agatoxins
  • Anesthetics, Local / pharmacology
  • Animals
  • Cadmium / pharmacology
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, P-Type / physiology
  • Calcium Channels, Q-Type / physiology
  • Cerebellum / cytology
  • Cerebellum / physiology
  • Chelating Agents / pharmacology
  • Dendrites / physiology*
  • Egtazic Acid / analogs & derivatives*
  • Egtazic Acid / pharmacology
  • Evoked Potentials / drug effects
  • Evoked Potentials / physiology
  • Organ Culture Techniques
  • Potassium Channel Blockers / pharmacology
  • Purkinje Cells / physiology*
  • Purkinje Cells / ultrastructure
  • Rats
  • Rats, Wistar
  • Spider Venoms / pharmacology
  • Tetraethylammonium / pharmacology
  • Tetrodotoxin / pharmacology

Substances

  • Agatoxins
  • Anesthetics, Local
  • Calcium Channel Blockers
  • Calcium Channels, P-Type
  • Calcium Channels, Q-Type
  • Chelating Agents
  • Potassium Channel Blockers
  • Spider Venoms
  • omega-agatoxin-Aa4b
  • Cadmium
  • 1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
  • Tetrodotoxin
  • Egtazic Acid
  • Tetraethylammonium
  • 4-Aminopyridine
  • Calcium