Browsing by Author "Hameed, Shahid"

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    D1 receptors physically interact with N-type calcium channels to regulate channel distribution and dendritic calcium entry
    (Elsevier, 2008-05-22) Kisilevsky, Alexandra E.; Mulligan, Sean J.; Altier, Christophe; Iftinca, Mircea C.; Varela, Diego L.; Tai, Chao; Chen, Lina; Hameed, Shahid; Hamid, Jawed; MacVicar, Brian Archibald; Zamponi, Gerald W.
    Dopamine signaling through D1 receptors in the prefrontal cortex (PFC) plays a critical role in the maintenance of higher cognitive functions, such as working memory. At the cellular level, these functions are predicated to involve alterations in neuronal calcium levels. The dendrites of PFC neurons express D1 receptors and N-type calcium channels, yet little information exists regarding their coupling. Here, we show that D1 receptors potently inhibit N-type channels in dendrites of rat PFC neurons. Using coimmunoprecipitation, we demonstrate the existence of a D1 receptor-N-type channel signaling complex in this region, and we provide evidence for a direct receptor-channel interaction. Finally, we demonstrate the importance of this complex to receptor-channel colocalization in heterologous systems and in PFC neurons. Our data indicate that the N-type calcium channel is an important physiological target of D1 receptors and reveal a mechanism for D1 receptor-mediated regulation of cognitive function in the PFC.
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    Glutamate receptors on myelinated spinal cord axons: I. GluR6 kainate receptors
    (Wiley-Liss, Inc., 2009-02) Ouardouz, Mohamed; Basak, Ajoy; Chen, Andrew; Rehak, Renata; Yin, Xinghua; Coderre, Elaine M.; Zamponi, Gerald W.; Hameed, Shahid; Trapp, Bruce D. T.; Stys, Peter K.
    The deleterious effects of glutamate excitotoxicity are well described for central nervous system gray matter. Although overactivation of glutamate receptors also contributes to axonal injury, the mechanisms are poorly understood. Our goal was to elucidate the mechanisms of kainate receptor-dependent axonal Ca(2+) deregulation.
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    Heterodimerization of ORL1 and opioid receptors and its consequences for N-type calcium channel regulation
    (The American Society for Biochemistry and Molecular Biology, Inc., 2010-01-08) You, Haitao; Hameed, Shahid; Altier, Christophe; Mezghrani, Alexandre; Bourinet, Emmanuel; Evans, Rhian M.; Zamponi, Gerald W.
    We have investigated the heterodimerization of ORL1 receptors and classical members of the opioid receptor family. All three classes of opioid receptors could be co-immunoprecipitated with ORL1 receptors from both transfected tsA-201 cell lysate and rat dorsal root ganglia lysate, suggesting that these receptors can form heterodimers. Consistent with this hypothesis, in cells expressing either one of the opioid receptors together with ORL1, prolonged ORL1 receptor activation via nociceptin application resulted in internalization of the opioid receptors. Conversely, mu-, delta-, and kappa-opioid receptor activation with the appropriate ligands triggered the internalization of ORL1. The mu-opioid receptor/ORL1 receptor heterodimers were shown to associate with N-type calcium channels, with activation of mu-opioid receptors triggering N-type channel internalization, but only in the presence of ORL1. Furthermore, the formation of opioid receptor/ORL1 receptor heterodimers attenuated the ORL1 receptor-mediated inhibition of N-type channels, in part because of constitutive opioid receptor activity. Collectively, our data support the existence of heterodimers between ORL1 and classical opioid receptors, with profound implications for effectors such as N-type calcium channels.
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    Intermediate conductance calcium-activated potassium channels modulate summation of parallel fiber input in cerebellar Purkinje cells
    (Proceedings of the National Academy of Sciences, 2012-02-14) Engbers, Jordan D .T.; Anderson, Dustin M.; Asmara, Hadhimulya; Rehak, Renata; Mehaffey, W. Hamish; Hameed, Shahid; McKay, Bruce E.; Kruskic, Mirna; Zamponi, Gerald W.; Turner, Ray W.
    Encoding sensory input requires the expression of postsynaptic ion channels to transform key features of afferent input to an appropriate pattern of spike output. Although Ca(2+)-activated K(+) channels are known to control spike frequency in central neurons, Ca(2+)-activated K(+) channels of intermediate conductance (KCa3.1) are believed to be restricted to peripheral neurons. We now report that cerebellar Purkinje cells express KCa3.1 channels, as evidenced through single-cell RT-PCR, immunocytochemistry, pharmacology, and single-channel recordings. Furthermore, KCa3.1 channels coimmunoprecipitate and interact with low voltage-activated Cav3.2 Ca(2+) channels at the nanodomain level to support a previously undescribed transient voltage- and Ca(2+)-dependent current. As a result, subthreshold parallel fiber excitatory postsynaptic potentials (EPSPs) activate Cav3 Ca(2+) influx to trigger a KCa3.1-mediated regulation of the EPSP and subsequent after-hyperpolarization. The Cav3-KCa3.1 complex provides powerful control over temporal summation of EPSPs, effectively suppressing low frequencies of parallel fiber input. KCa3.1 channels thus contribute to a high-pass filter that allows Purkinje cells to respond preferentially to high-frequency parallel fiber bursts characteristic of sensory input.