RESUMEN
Abnormal synchronous neuronal activity has been widely detected by brain imaging of autistic patients, but its underlying neural mechanism remains unclear. Compared with wild-type mice, our in vivo two-photon imaging showed that transgenic (Tg1) mice over-expressing human autism risk gene MeCP2 exhibited higher neuronal synchrony in the young but lower synchrony in the adult stage. Whole-cell recording of neuronal pairs in brain slices revealed that higher neuronal synchrony in young postnatal Tg1 mice was attributed mainly to more prevalent giant slow inward currents (SICs). Both in vivo and slice imaging further demonstrated more dynamic activity and higher synchrony in astrocytes from young Tg1 mice. Blocking astrocytic gap junctions markedly decreased the generation of SICs and overall cell synchrony in the Tg1 brain. Furthermore, the expression level of Cx43 protein and the coupling efficiency of astrocyte gap junctions remained unchanged in Tg1 mice. Thus, astrocytic gap junctions facilitate but do not act as a direct trigger for the abnormal neuronal synchrony in young Tg1 mice, revealing the potential role of the astrocyte network in the pathogenesis of MeCP2 duplication syndrome.
RESUMEN
AIM To study the effects of Lotusine(Lot), a pure alkaloid extracted from the green seed embryo of Nelumbo nucifera Gaertn, on the action potentials(APs) in myocardium and slow inward current(Isi) in cardiac Purkinje fibers(PF). METHODS standard microelectrode and two microelectrodes voltage clamp techniques were used. RESULTS Lot 1～100 ?mol?L -1 could concentration dependently prolonged APD 20 and APD 90 of fast AP and increase the contractile force(Fc) in guinea pig papillary muscles. In papillary muscles pretreated with reserpine, similar results were also observed but the effect of Lot was weaker than those pretreated without reserpine. In guinea pig left atria, Lot 30 ?mol?L -1 could partly antigoniste the shortening APD effect of acetylcholine. Lot 3～100 ?mol?L -1 could enhance the action potential amplitude(APA)and maximal velocity of phase 0 depolarization ( V max ) of slow AP of papillary muscles induced by high K + (24 mmol?L -1 )and isolated sinoatral node(SAN) pacemaker cells of rabbits with dose dependent manner,But not obvousely short the sinus cycle length of SAN. Moreover, Lot increased the Isi of in canin cardiac PF with with time dependent and dose dependent manner. CONCLUSION The results suggest that Lot has effect of prolongation of APD and increase of Ca 2+ influx and these are very important in contribution to its positive inotropic effect, which may be related to inhibition of phosphodiesterase Ⅲ.