• Activity of T-type calcium channels is independent of CRMP2 in sensory neurons

      Cai, Song; Shan, Zhiming; Zhang, Zhongjun; Moutal, Aubin; Khanna, Rajesh; Univ Arizona Hlth Sci, Coll Med, Dept Pharmacol (TAYLOR & FRANCIS INC, 2019-04-26)
      Amongst the regulators of voltage-gated ion channels is the collapsin response mediator protein 2 (CRMP2). CRMP2 regulation of the activity and trafficking of NaV1.7 voltage-gated sodium channels as well as the N-type (CaV2.2) voltage-gated calcium channel (VGCC) has been reported. On the other hand, CRMP2 does not appear to regulate L- (CaV1.x), P/Q- (CaV2.1), and R- (CaV2.3) type high VGCCs. Whether CRMP2 regulates low VGCCs remains an open question. Here, we asked if CRMP2 could regulate the low voltage-gated (T-type/CaV3.x) channels in sensory neurons. Reducing CRMP2 protein levels with short interfering RNAs yielded no change in macroscopic currents carried by T-type channels. No change in biophysical properties of the T-type currents was noted. Future studies pursuing CRMP2 druggability in neuropathic pain will benefit from the findings that CRMP2 regulates only the N-type (CaV2.2) calcium channels.
    • Involvement of T-type calcium channels in the mechanism of low dose morphine-induced hyperalgesia in adult male rats

      Abbasloo, Elham; Abdollahi, Farzaneh; Saberi, Arezoo; Esmaeili-Mahani, Saeed; Kaeidi, Ayat; Akhlaghinasab, Fereshteh; Sheibani, Vahid; Thomas, Theresa Currier; Kobeissy, Firas Hosni; Oryan, Shahrbanoo; et al. (Elsevier BV, 2021-12)
      It has been shown that systemic and local administration of ultra-low dose morphine induced a hyperalgesic response via mu-opioid receptors. However, its exact mechanism(s) has not fully been clarified. It is documented that mu-opioid receptors functionally couple to T-type voltage dependent Ca+2 channels. Here, we investigated the role of T-type calcium channels, amiloride and mibefradil, on the induction of low-dose morphine hyperalgesia in male Wistar rats. The data showed that morphine (0.01 μg i.t. and 1 μg/kg i.p.) could elicit hyperalgesia as assessed by the tail-flick test. Administration of amiloride (5 and 10 μg i.t.) and mibefradil (2.5 and 5 μg i.t.) completely blocked low-dose morphine-induced hyperalgesia in spinal dorsal horn. Amiloride at doses of 1 and 5 mg/kg (i.p.) and mibefradil (9 mg/kg ip) 10 min before morphine (1 μg/kg i.p.) inhibited morphine-induced hyperalgesia. Our results indicate a role for T-type calcium channels in low dose morphine-induced hyperalgesia in rats.