Synaptic alterations at the calyx of Held in S218L KI mice mutant of Cav 2.1 Ca2+ channel responsible of familial hemiplegic migraine type 1 decease in humans

DI GUILMI, MN; GONZÁLEZ INCHAUSPE, C; VAN DEN MAAGDENBERG; FRANTS RR; FERRARI MD; UCHITEL O.D

Buzios, Brazil

Congreso; I CONGRESSO IBRO/LARC DE NEUROCIÊNCIAS DA AMÉRICA LATINA, CARIBE E PENÍNSULA IBÉRICA (NEUROLATAM); 2008

Familial hemiplegic migraine type-1 (FHM1) is a Mendelian subtype of migrainethat is caused by missense mutations in the CACNA1A gene. Cav2.1 (P/Q-type)calcium channels are located throughout the mammalian nervous system atpresynaptic terminals, where they play a prominent role in controllingneurotransmitter release. We used knockin transgenic mice with the pathogenicFHM1 human mutation S218L (Tottone A et. al. 2005) to investigate presynapticcalcium currents and transmitter release. We used auditory brainstem slicescontaining the Medial Nucleus of the Trapezoid Body (MNTB), whose principalneurons receive a giant synapse (calyx of Held).We used wild type (WT) andmutant mice (MM). Using whole-cell configuration a little shift was found in theI-V curve to more negative potentials (WT: -10 mV; MM: -15 mV). Related tothe spontaneous events, the frequency and amplitude was highest in the mutantmice in comparison with the wild type. The mean frequency was WT: 2.03±0.55and MM: 4.29±1.07. Related to the amplitude, not clear difference existsbetween both groups (WT: 45±3pA and MM:45.82±1.3pA). In the other hand,some cells of the MM animals presented height frequency and low amplitude orvice versa (mean amplitude in the last group was 201.55±9.19pA). A jitter wasproduce in a group of MM under stimulation in the middle line with a bipolarelectrode. These results could be indicating that the mutation could producealterations in the synaptic transmission at the calyx of Held and provideimportant information to understand the basic features of the physiology ofneurological disease such as migraine.