OBJECTIVE: The present study was aimed to investigate the pharmacological modulatory effects of ropivacaine, an amide-type local anesthetic, on rat Nav1.2 (rNav1.2) and rNav1.5, the two Na(+) channel isoforms heterologously expressed in Xenopus oocytes and in HEK293t cell line, respectively. METHODS: Two-electrode voltage-clamp (TEVC) and whole-cell patch-clamp recordings were employed to record the whole-cell currents. RESULTS: Ropivacaine induced tonic inhibition of peak Na(+) currents of both subtypes in a dose- and frequency-dependent manner. rNav1.5 appeared to be more sensitive to ropivacaine. In addition, for both Na(+) channel subtypes, the steady-state inactivation curves, but not the activation curves, were significantly shifted to the hyperpolarizing direction by ropivacaine. Use-dependent blockade of both rNav1.2 and rNav1.5 channels was induced by ropivacaine through a high frequency of depolarization, suggesting that ropivacaine could preferentially bind to the 2 inactivated Na(+) channel isoforms. CONCLUSION: The results will be helpful in understanding the pharmacological modulation by ropivacaine on Nav1.2 subtype in the central nervous system, and on Nav1.5 subtype abundantly expressed in the heart.
OBJECTIVE: The present study was aimed to investigate the pharmacological modulatory effects of ropivacaine, an amide-type local anesthetic, on ratNav1.2 (rNav1.2) and rNav1.5, the two Na(+) channel isoforms heterologously expressed in Xenopus oocytes and in HEK293t cell line, respectively. METHODS: Two-electrode voltage-clamp (TEVC) and whole-cell patch-clamp recordings were employed to record the whole-cell currents. RESULTS:Ropivacaine induced tonic inhibition of peak Na(+) currents of both subtypes in a dose- and frequency-dependent manner. rNav1.5 appeared to be more sensitive to ropivacaine. In addition, for both Na(+) channel subtypes, the steady-state inactivation curves, but not the activation curves, were significantly shifted to the hyperpolarizing direction by ropivacaine. Use-dependent blockade of both rNav1.2 and rNav1.5 channels was induced by ropivacaine through a high frequency of depolarization, suggesting that ropivacaine could preferentially bind to the 2 inactivated Na(+) channel isoforms. CONCLUSION: The results will be helpful in understanding the pharmacological modulation by ropivacaine on Nav1.2 subtype in the central nervous system, and on Nav1.5 subtype abundantly expressed in the heart.
Authors: D Zaric; K Axelsson; L Philipson; P A Nydahl; P Larsson; J R Jansson; P Leissner Journal: Acta Anaesthesiol Scand Date: 1993-04 Impact factor: 2.105
Authors: C Stoetzer; T Doll; T Stueber; C Herzog; F Echtermeyer; F Greulich; C Rudat; A Kispert; F Wegner; A Leffler Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2016-03-22 Impact factor: 3.000