Experimental Physiology –Research Paper: Modulation of N‐type calcium currents by presynaptic imidazoline receptor activation in rat superior cervical ganglion neurons

Abstract

Presynaptic imidazoline receptors (R i-pre ) are found in the sympathetic axon terminals of animal and human cardiovascular systems, and they regulate blood pressure by modulating the release of peripheral noradrenaline (NA). The cellular mechanism of R i-pre -induced inhibition of NA release is unknown. We, therefore, investigated the effect of R i-pre activation on voltage-dependent Ca 2+ channels in rat superior cervical ganglion (SCG) neurons, using the conventional whole-cell patch-clamp method. Cirazoline (30 μm), an R i-pre agonist as well as an α-adrenoceptor (R α ) agonist, decreased Ca 2+ currents (I Ca ) by about 50% in a voltage-dependent manner with prepulse facilitation. In the presence of low-dose rauwolscine (3 μm), which blocks the α 2 -adrenoceptor (R α2 ), cirazoline still inhibited I Ca by about 30%, but prepulse facilitation was significantly attenuated. This inhibitory action of cirazoline was almost completely prevented by high-dose rauwolscine (30 μm), which blocks R i-pre as well as R α2 . In addition, pretreatment with LY320135 (10 μm), another R i-pre antagonist, in combination with low-dose rauwolscine (3 μm), also blocked the R α2 -resistant effect of cirazoline. Addition of guanosine-5 -O-(2-thiodiphosphate) (2 mm) to the internal solutions significantly attenuated the action of cirazoline. However, pertussis toxin (500 ng ml −1 ) did not significantly influence the inhibitory effect of cirazoline. Moreover, cirazoline (30 μm) suppressed M current in SCG neurons cultured overnight. Finally, ω-conotoxin (ω-CgTx) GVIA (1 μm) obstructed cirazolineinduced current inhibition, and cirazoline (30 μm) significantly decreased the frequency of action potential firing in a partly reversible manner. This cirazoline-induced inhibition of action potential firing was almost completely occluded in the presence of ω-CgTx. Taken together, our results suggest that activation of R i-pre in SCG neurons reduced N-type I Ca in a pertussis toxinand voltage-insensitive pathway, and this inhibition attenuated repetitive action potential firing in SCG 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.…”

Noradrenaline Modulates the Membrane Potential and Holding Current of Medial Prefrontal Cortex Pyramidal Neurons via β1-Adrenergic Receptors and HCN Channels

“…The amplitude of the cirazoline-dependent hyperpolarization in the presence of an α 1 -adrenergic receptor blocker prazosin in the bath (100 μM, Kobayashi, 2007 ; Luo et al, 2014 , Figures 3Ca,b ) was not significantly different than that in the presence of cirazoline alone (-4.4 ± 0.5 mV, n = 6, p = 0.2344, unpaired t -test). Cirazoline can activate imidazoline receptors ( Chung et al, 2010 ). Therefore, the effect of cirazoline on the membrane potential was tested in the presence of an imidazoline receptor antagonist efaroxan (100 μM).…”

Dexmedetomidine and clonidine inhibit the function of NaV1.7 independent of α2-adrenoceptor in adrenal chromaffin cells

“…channels is unclear, it is known that voltage-dependent Ca 2? channels are inhibited by imidazoline receptor activation in rat cervical ganglion neurons or hippocampal neurons [48,49]. Thus, it is possible that the inhibitory effects of a 2 -agonists and a 2 -antagonists that contain an imidazole ring on Na ?…”