Modulation of N-type Ca2+ currents by moxonidine via imidazoline I1 receptor activation in rat superior cervical ganglion neurons

Inhibitory effects of imidazoline receptor ligands on basal and kainic acid-induced neurotoxic signalling in mice

“…Dong et al, 2009;Lai et al, 2014). Previous studies have reported reduced Ca 2+ -influx through reversible blockade of NMDARs and N-type Ca 2+ currents after I 2 -or I 1 -IR ligands, respectively (Chung et al, 2010;Han et al, 2013;Jiang et al, 2010;Kim et al, 2011;Olmos, DeGregorio-Rocasolano, et al, 1999;Olmos, Ribera, et al, 1996; see Figure 6). Thus, in agreement with a recent report (Jiang et al, 2010), the inhibitory effects of IR drugs on calpain activity (reduced fragmentation of spectrin α and p35) appear to result from decreased intracellular Ca 2+ concentrations and not from direct enzyme inhibition.…”

“…Garau et al, 2013;Haxhiu et al, 1994;Kim et al, 2011;Sánchez-Blázquez et al, 2000;Thorn et al, 2012), and efaroxan (I 1 -IR) and idazoxan (I 2 -IR) as IR antagonists to prevent the effects of moxonidine and LSL61122, respectively (e.g. see Cambridge and Robinson, 2005;Haxhiu et al, 1994;Sánchez-Blázquez et al, 2000).…”

“…Besides sympatho-inhibitory (I 1 -IR-mediated) and insulin-secretory (pancreatic I 3 -IR-mediated) actions (Bousquet et al, 1984; Chan et al, 1994), putative IR agonists, such as moxonidine (I 1 -selective), BU224 (I 2 -selective) and LSL61122 (mixed I 1 /I 2 -ligand), may have therapeutic potential in various neurological disorders (García-Sevilla et al, 1999; Gupta and Sharma, 2014; Keller and García-Sevilla, 2015a; Li et al, 2012; Piletz, et al, 2000). Notably, I 1 - and I 2 -IR ligands have been shown to exert neuroprotection through reversible blockade of N-methyl-D-aspartate (NMDA) receptors (Han et al, 2013; Jiang et al, 2010; Milhaud et al, 2000; Olmos, DeGregorio-Rocasolano, et al, 1999; Olmos, Ribera, et al, 1996) and activation of presynaptic IRs that can inhibit N-type calcium (Ca 2+ ) currents and repetitive action potential firing (Chung et al, 2010; Kim et al, 2011). Moreover, IR drugs and the I 1 -IR candidate IR antisera-selected (IRAS)/nischarin (Alahari et al, 2000; Piletz, et al, 1999) have been associated with anti-apoptotic and/or cytoprotective functions, as they were shown to reduce the contents of pro-apoptotic proteins and to protect cells from cell death induced by noxious stimuli (Choi et al, 2002; Dontenwill et al, 2003; Garau et al, 2013).…”

Immunodetection and subcellular distribution of imidazoline receptor proteins with three antibodies in mouse and human brains: Effects of treatments with I1- and I2-imidazoline drugs

“…In fact, treatments of rats with I 2 -drugs upregulated cortical GFAP content in parallel with the density of I 2 -sites (Olmos et al, 1994), indicating a direct role of I 2 -IR in the induction of astrogliosis (Casanovas et al, 2000). On the other hand, recent electrophysiological (whole-cell patch-clamp) studies revealed the localization of I 1 -IRs in rat superior cervical ganglion neurones, which were activated by moxonidine and blocked by efaroxan (Kim et al, 2011).…”

Use of Patch Clamp Electrophysiology to Identify Off-Target Effects of Clinically Used Drugs

“…Immortalized or primary cell culture models that retain expression of the same ion channels that are natively expressed in the tissue under investigation should be considered. Some examples include neonatal cardiomyocytes for studying cardiac ion channel function (Markandeya et al, 2011), rat superior cervical ganglion (SCG) neurons for natively expressed neuronal ion channels (Kim et al, 2011;Zaika et al, 2011), and embryonic www.intechopen.com rat aortic (A7r5 and A10) cell lines for investigating vascular smooth muscle electrophysiology (Roullet et al, 1997;Brueggemann et al, 2005;Brueggemann et al, 2007). The advantages of using cultured cells compared with freshly dissociated cells from the native tissue include their accessibility, ease of maintenance, high experimental reproducibility, and susceptibility to molecular interventions.…”