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• W1973707587 startingPage "905" @default.
• W1973707587 abstract "The aim of this work is to characterise the functional properties of human and rat NaV1.8 channels and to investigate the action of anti-nociceptive agents. NaV1.8 α-subunits were expressed in mammalian sensory neuron-derived ND7/23 cells, and sodium currents were recorded using whole-cell patch clamp. The current–voltage curves for activation were similar for human and rat NaV1.8 channels. However, for inactivation, human NaV1.8 showed more hyperpolarised voltage-dependence than for the rat channel, faster development of inactivation, slower recovery from the fast component of inactivation, and faster recovery from the slow component. Thus, this would imply that the human channel is more inactivated at normal resting potentials. Compounds 227c89, A-803467, V102862, ralfinamide and tetracaine all showed greater affinity for the inactivated state than for the resting state. Compounds A-803467 and V102862 were the most potent, and A-803467 showed greater inactivated state affinity for human than for rat channels. Surprisingly, during recovery from inactivation, an increase in current was observed for V102862 and A-803467, probably due to disinhibition of resting block. Rather than the use-dependent inhibition normally seen with inactivated state blockers, for A-803467 this disinhibition led to an increase in current during repetitive stimulation, while V102862 showed less inhibition than otherwise expected at lower frequencies. Thus the data supports the suggestion that, while both V102862 and A-803467 are potent inhibitors of NaV1.8, the compound V102862, rather than A-803467, may be useful as an analgesic where physiological firing frequencies are higher." @default.
• W1973707587 created "2016-06-24" @default.
• W1973707587 creator A5056579783 @default.
• W1973707587 creator A5063064965 @default.
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• W1973707587 date "2009-04-01" @default.
• W1973707587 modified "2023-09-23" @default.
• W1973707587 title "Functional and pharmacological properties of human and rat NaV1.8 channels" @default.
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• W1973707587 doi "https://doi.org/10.1016/j.neuropharm.2009.01.018" @default.
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