Modulation of inhibitory post-synaptic currents (IPSCs) in mouse cerebellar Purkinje and basket cells by snake and scorpion toxin K⁺ channel blockers

Abstract

1. Using an in vitro mouse cerebellar slice preparation and whole-cell electrophysiological recording techniques we have characterized Purkinje and basket cell inhibitory post-synaptic currents (IPSCs), and examined the effects of a number of selective peptidergic K⁺ channel blockers.

2. Spontaneous IPSC amplitude ranged from ∼10 pA up to ∼3 nA for both cell types [mean values: Purkinje cells −122.8±20.0 pA (n=24 cells); basket cells −154.8±15.9 pA (n=26 cells)]. Frequency varied from ∼3 up to ∼40 Hz, [mean values: basket cells 14.9±1.7 Hz (n=26 cells); Purkinje cells 17.9±2.2 Hz (n=24 cells)]. 5 μM bicuculline eliminated virtually all spontaneous currents.

3. IPSC rise times were fast (∼0.6 ms) and the decay phase was best fit with the sum of two exponential functions (τ₁ and τ₂: ∼4 ms and ∼20 ms, n=40; for both cell types).

4. The snake toxins alpha-dendrotoxin (α-DTX) and toxin K greatly enhanced IPSC frequency and amplitude in both cell types; the closely related homologues toxin I and gamma-dendrotoxin (γ-DTX) produced only marginal enhancements (all at 200 nM).

5. Two scorpion toxins, margatoxin (MgTX) and agitoxin-2 (AgTX-2) had only minor effects on IPSC frequency or amplitude (both at 10 nM).

6. Low concentrations of tetraethylammonium (TEA; 200 μM) had no overall effect on cerebellar IPSCs, whilst higher concentrations (10 mM) increased both the frequency and amplitude.

7. The results suggest that native K⁺ channels, containing Kv1.1 and Kv1.2 channel subunits, play an influential role in controlling GABAergic inhibitory transmission from cerebellar basket cells.

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