Abstract
In single isolated guinea pig ventricular cardiomyocytes, 8-(N,N-diethylamino)-octyl-3, 4, 5-trimethoxybenzoate hydrochloride (TMB-8) nonselectively inhibited membrane currents. TMB-8 concentration dependently and reversibly reduced calcium current (ICa) (pD2 5.0). The Ca++ channel blockade was only slightly use dependent. The steady-state inactivation curve of ICa was shifted to more negative membrane potentials by TMB-8; the curve for the normalized conductance of ICa was not significantly affected. The quasi steady-state K+ currents as a measure for K+ conductance were examined by means of slow depolarizing ramp pulses between -120 and +60 mV. In this potential range. TMB-8 (100 microM) reduced quasi steady-state potassium currents. The sodium current sodium current (INa) was investigated at low extracellular Na+ concentration (30 mM) after blocking ICa by Cd++ and reducing K+ currents (Cs+ substituted for K+). Under these conditions, TMB-8 concentration dependently and reversibly decreased INa (pD2 5.3), slightly shifted the steady-state inactivation curve of INa to more negative potentials and shifted the curve for the normalized conductance of INa to more positive potentials. We conclude that TMB-8 possesses both Ca++ channel- and Na+ channel-blocking properties and reduces the membrane K+ conductance. It is speculated that, because of its amphiphilic nature, TMB-8 accumulates at lipid-water interphase of biologic membranes and therefore interferes with the normal function of many membrane proteins.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|