Open AccessExpression of cardiac Na channels with appropriate physiological and pharmacological properties in Xenopus oocytes.
Author(s) -
Douglas S. Krafte,
Walter A. Volberg,
Kathleen Dillon,
Alan M. Ezrin
Publication year - 1991
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.88.10.4071
Subject(s) - xenopus , tetrodotoxin , oocyte , sodium channel , biophysics , ic50 , guinea pig , chemistry , pharmacology , endocrinology , biology , medicine , sodium , microbiology and biotechnology , in vitro , biochemistry , gene , embryo , organic chemistry
The objective of this study was to determine whether the Xenopus laevis oocyte can express an exogenous cardiac Na channel that retains its normal physiological and pharmacological properties. Cardiac Na channels were expressed in oocytes following injection of RNA from guinea pig, rat, and human heart and detailed analysis was performed for guinea pig cardiac Na channels. Average current amplitudes were -351 +/- 37 nA with peak current observed at -8 +/- 1 mV. Steady-state inactivation was half-maximal at -49 +/- 0.6 mV for the expressed channels. All heart Na currents were resistant to block by tetrodotoxin compared to Na currents expressed from brain RNA with IC50 values for guinea pig, rat, and human heart of 651 nM, 931 nM, and 1.3 microM, respectively. In contrast, rat brain Na channels were blocked by tetrodotoxin with an IC50 value of 9.1 nM. In addition, the effects of the cardiac-selective agents lidocaine and DPI 201-106 were examined on Na currents expressed from brain and heart RNA. Lidocaine (10 microM) blocked cardiac Na current in a use-dependent manner but had no effect on brain Na currents. DPI 201-106 (10 microM) slowed the rate of cardiac Na channel inactivation but had no effect on inactivation of brain Na channels. These results indicate the Xenopus oocyte system is capable of synthesizing and expressing cardiac Na channels that retain normal physiological and pharmacological properties.