Reduction of presynaptic calcium influx with higher amplitude excitatory post-synaptic currents in S218L Cav 2.1 knock-in migraine mouse model

DI GUILMI MN; GONZALEZ INCHAUSPE C; URBANO FJ; FORSYTHE ID; VAN DEN MAAGDENBERG A; BORST JG; UCHITEL OD

Huerta Grande, Cordoba

Congreso; XXVI Congreso Anual de la Sociedad Argentina de Investigacion en Neurociencia; 2011

Sociedad Argentina de Investigación en Neurociencia

We used KI S218L mice to study Ca2+ currents and excitatory postsynaptic currents (EPSCs) at the calyx of Held. During whole-cell patch-clamp recordings, a shift of the peak of the I-V curve to more negative potentials was observed. Steady-state activation curves were also significantly shifted between WT and KI mice, activating at more negative potentials in KI. On the other hand, presynaptic calcium currents (IpCa) evoked by action potential (AP) waveforms had less amplitude in KI than WT. Additionally, Ca2+ current facilitation after 100 Hz train of APs was significant reduced in KI compared to WT mice. Both EPSC amplitudes and miniature EPSC frequencies were significant higher in KI than WT. The synaptic activity in the KI showed less rate of short term depression with a faster recovery after either 10 or 100 Hz frequency trains. Our results suggest that the calcium channel activation shift might be increasing calcium influx at resting membrane potential. Such calcium concentration increment would lead to a decrement in action potential-induced calcium influx due to channel inactivation. Moreover, an acceleration of calcium dependent process on the exocitosis machinery might explain the observe increment in EPSC amplitude regardless of the observed reduction in IpCa.