Various voltage-gated K+ currents were recently described in dorsal root ganglion (DRG) neurons. However, the characterization and diversity of voltage-gated K+ currents have not been well studied in trigeminal root ganglion (TRG) neurons, which are similar to the DRG neurons in terms of physiological roles and anatomy. This study was aimed to investigate the characteristics and diversity of voltage-gated K+ currents in acutely isolated TRG neurons of rat using whole cell patch clamp techniques. The first type (type I) had a rapid, transient outward current (IA) with the largest current size having a slow inactivation rate and a sustained delayed rectifier outward current (IK) that was small in size having a fast inactivation rate. The IA currents of this type were mostly blocked by TEA and 4-AP, K channel blockers whereas the IK current was inhibited by TEA but not by 4-AP. The second type had a large IA current with a slow inactivation rate and a medium size-sustained delayed IK current with a slow inactivation rate. In this second type (type II), the sensitivities of the IA or IK current by TEA and 4-AP were similar to those of the type I. The third type (type III) had a medium sized IA current with a fast inactivation rate and a large sustained IK current with the slow inactivation rate. In type III current, TEA decreased both IA and IK but 4-AP only blocked IA current. The fourth type (type IV) had a smallest IA with a fast inactivation rate and a large IK current with a slow inactivation rate. TEA or 4-AP similarly decreased the IA but the IK was only blocked by 4-AP. These findings suggest that at least four different voltage-gated K+ currents in biophysical and pharmacological properties exist in the TRG neurons of rats.
The working mechanism of bisphosphonate on bone cells is unclear despite its powerful inhibitory activity on bone resorption. The differentiation and activation of osteoclasts are essential for bone resorption and are controlled by the stimulatory RANKL and inhibitory OPG molecules. Teeth exhibit a range of movement patterns during their eruption to establish their form and function, which inevitably accompanies peripheral bone resorption. Hence, the mandible, which contains the teeth during their eruption processes, is a good model for revealing the inhibitory mechanism of bisphosphonate upon bone resorption. In the present study, RANKL and OPG expression were examined immunohistochemically in the mandible of rats with developing teeth after alendronate administration (2.5 mg/kg). The preeruptive mandibular first molars at postnatal days 3 to 10 showed the developing stages from bell to crown. No morphological changes in tooth formation were observed after alendronate administration. The number of osteoclasts in the alveolar bone around the developing teeth decreased markedly at postnatal days 3, 7 and 10 compared with the control group. RANKL induced strong positive immunohistochemical reactions in the dental follicles and stromal cells around the mandibular first molar. In particular, many osteoclasts with strongly positive reactions to RANKL appeared above the developing mandibular first molars at postnatal days 3 and 10. Immunohistochemical reactions with RANKL after alendronate administration were weaker than the control groups. However, the immunohistochemical reactivity to OPG was stronger after alendronate administration, at postnatal days 3 and 10. These results suggest that alendronate may decrease bone resorption by regulating the RANKL/OPG pathway in the process of osteoclast formation, resulting in a delay in tooth eruption.