Changes of the peripheral nerve excitability in vivo induced by the persistent Na+ current blocker ranolazine

Neuroscience Letters
Hiroyuki Nodera, Seward Rutkove

Abstract

Persistent Na(+) current (Na(p)) in the peripheral axons play an important functional role in controlling the axonal excitability. Abnormal Na(p) is believed to contribute to neurodegeneration and neuropathic pain, and thus it is an attractive therapeutic target. To assess the behavior of selective Na(p) blockade, axonal excitability testing was performed in vivo in 10 normal male mice exposed to ranolazine by recording the tail sensory nerve action potentials (SNAPs). Twenty minutes after administering ranolazine i.p. (50 mg/kg), the following changes were observed: lower SNAP amplitudes and the need for greater stimulus currents; greater threshold changes induced by long hyperpolarizing currents; reduced accommodation to long depolarizing current along with reduced late subexcitability; and reduced strength-duration time constant. These changes are explained by the suppression of Na(p) leading to greater threshold currents, partial block of transient Na(+) current, and suppression of slow K(+) currents. The suppressed slow K(+) currents appear to limit the modification of the membrane excitability by ranolazine. This study confirms the utility of axonal excitability testing as a useful treatment biomarker in neurological cond...Continue Reading

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Citations

Feb 26, 2016·Frontiers in Physiology·Chimeglkham BanzraiRyuji Kaji
Jul 25, 2012·Neuroscience Letters·Hiroyuki Nodera, Seward B Rutkove
Dec 3, 2015·Neuroscience Letters·Chimeglkham BanzraiRyuji Kaji
Oct 12, 2014·Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology·Yoshimitsu ShimataniRyuji Kaji
Jun 20, 2018·Journal of the Peripheral Nervous System : JPNS·Preet G S MakkerJames Howells
Jun 4, 2014·PloS One·Delphine BoërioWerner J Z'Graggen

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