正常和MPTP帕金森病模型小鼠苍白球HCN通道的电生理学研究.pdfVIP

Electrophysiological studies of HCN channels in the globus pallidus of both normal and MPTP parkinsonian mice Abstract The globus pallidus rGPl iS an important relay nucleus located centrally in the basal ganglia，which plays a key role in multiple feedback loops in both health and pathological states．Recent studies have reported that hyperpolarization activated cyclic—nucleotide gated (HCN)channels occupies a significant position in globus pallidus pacemaking activity． Morphological studies have shown that HCN channels are expressed in the globus pallidus． Previous in vitro patch clamp recordings revealed that blockade of HCN channels significantly changes the spontaneous firing of globus pallidus neurons． Object：To evaluate the electrophysiological effects of HCN channel biocker ZD7288 and／or CsCI on the spontaneous firing of globus pallidus neurons，as well as the expression ofHCN channels in both normal and MPTP—treated parkinsonian mice． Methods：／n vivo extracellular single unit recordings．MPTP parkinsonian mice and immunohistochemical staining were performed in the present study． Results：1．In normal mice，the spontaneous firing activity of 77 pallidal neurons were recorded．The average frequency of spontaneous firing was 7．9士O．8 Hz．Three firing pattern of globus pallidus neurons in mice were recorded，wiⅡ1 20(25．4％)regular firing neurons， 43(56．3％)irregular firing neurons and 14(1 8．3％)burst firing neurons．2．In normal mice, micro-pressure ejection of 0．05mM ZD7288 decreased me frequency of spontaneous firing from 9．84-1．5 Hz to 5．04-0．9 Hz in 30 out ofthe 58(51．7％1 neurons．The average decrease was 54．04-5．1％(P0．001)．Further firing pattem analysis showed that ZD7288 increased bom CV(Basal：0．82士0．14；ZD7288：1．39+0．19：P0．001)and FF(Basal：0．29士0．12： ZD7288：1．574-0．49；P0．001)，suggesting that ZD7288 decreased the firing regularity of neurons．In another 22(37．9％)pallidal neurons with the basal firing rate of 5．94-1．3 Hz， ZD7288 increased the firing rate to 10．8土2．1 Hz．The