TMB-8 as a pharmacologic tool in guinea pig myocardial tissues. II. Effects of TMB-8 on membrane currents in isolated ventricular cardiomyocytes.
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.
Pharmakologisches Institut, Universitaet-Gesamthochschule Essen, Germany.
H M
HM
Himmel
U
U
Ravens
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007473:Ion Channels; D015222:Sodium Channels; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D011188:Potassium