Acute modulation of calcium currents and synaptic transmission by gabapentinoids

UCHITEL OD ; DI GUILMI MN; URBANO FJ; GONZALEZ-INCHAUSPE C

CHANNELS

LANDES BIOSCIENCE

Lugar: Austin, Texas, USA; Año: 2010 vol. 4 p. 490 - 496

1933-6950

Gabapentin and pregabalin are anticonvulsant drugs that are extensively used for the treatment of several neurological and psychiatric disorders. Gabapentinoids (GBPs) are known to have a high affinity binding to alpha2delta1 and alpha2delta2 auxiliary subunit of specific voltage-gated calcium channels. Despite the confusing effects reported on Ca2+ currents, most of the studies showed that GBPs reduced release of various neurotransmitters from synapses in several neuronal tissues. We showed that acute in vitro application of pregabalin could reduce in a dose dependent manner synaptic transmission in both neuromuscular junctions and calyx of Held-MNTB excitatory synapses. Furthermore presynaptic Ca2+ currents treated with pregabalin are reduced in amplitude, do not show inactivation at a clinically relevant low concentration of 100 microM and activate and deactive faster. These results suggest novel modulatory role of acute pregabalin that might contribute to better understanding its anticonvulsant/analgesic clinical effects.