Expression and functions of N-type Cav2.2 and T-type Cav3.1 channels in rat vasopressin neurons under normotonic conditi
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e Journal of Physiological Sciences Open Access
ORIGINAL PAPER
Expression and functions of N‑type Cav2.2 and T‑type Cav3.1 channels in rat vasopressin neurons under normotonic conditions Kaori Sato‑Numata1,2, Tomohiro Numata2, Yoichi Ueta3 and Yasunobu Okada4*
Abstract Arginine vasopressin (AVP) neurons play essential roles in sensing the change in systemic osmolarity and regulating AVP release from their neuronal terminals to maintain the plasma osmolarity. AVP exocytosis depends on the C a2+ 2+ entry via voltage-gated C a channels (VGCCs) in AVP neurons. In this study, suppression by siRNA-mediated knock‑ down and pharmacological sensitivity of VGCC currents evidenced molecular and functional expression of N-type Cav2.2 and T-type Cav3.1 in AVP neurons under normotonic conditions. Also, both the Cav2.2 and Cav3.1 currents were found to be sensitive to flufenamic acid (FFA). TTX-insensitive spontaneous action potentials were suppressed by FFA and T-type VGCC blocker Ni2+. However, Cav2.2-selective ω-conotoxin GVIA failed to suppress the firing activ‑ ity. Taken together, it is concluded that Cav2.2 and Cav3.1 are molecularly and functionally expressed and both are sensitive to FFA in unstimulated rat AVP neurons. Also, it is suggested that Cav3.1 is primarily involved in their action potential generation. Keywords: Cav channel, Vasopressin neuron, Flufenamic acid, Action potential Background Arginine vasopressin (AVP) neurons that are located at the supraoptic nucleus (SON) and paraventricular nucleus (PVN) in the hypothalamus of the brain are a key player in maintaining the osmolarity of body fluid in a narrow range around 300 mOsm by secreting AVP from their neuronal terminals at the posterior pituitary gland. The action potential firing involves activation of Na+ and C a2+ conductance in the magnocellular neurosecretory cells (MNCs) consisting of AVP neurons and oxytocin (OXT) neurons [1–3]. The amount of vesicular exocytotic release of AVP from neurohypophysial terminals of MNCs is determined by the frequency and pattern of action potential firing [4] and by the entry of
*Correspondence: [email protected] 4 National Institute for Physiological Sciences, 5‑1 Higashiyama, Myodaiji, Okazaki, Aichi 444‑8787, Japan Full list of author information is available at the end of the article
Ca2+ via voltage-gated Ca2+ channels (VGCCs or Cav channels) [5]. Somatodendritic expression of L-, T- and N-type VGCCs in rat supraoptic AVP neurons was suggested based on pharmacological studies on the increases in the intracellular free C a2+ concentration ([Ca2+]i) in response to application of AVP [6] and pituitary adenylate cyclase-activating polypeptide (PACAP) [7]. Besides, nifedipine-sensitive L-type C a2+ currents were found to be increased in rat supraoptic MNCs under dehydration conditions produced after water deprivation for 16–24 h [8]. However, it is not known which types of VGCCs are expressed and functioning during the spontaneous action potential firing in unstimulated rat AVP neurons under normo
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