Barnidipine block of L-type Ca(2+) channel currents in rat ventricular cardiomyocytes.
The effects of barnidipine and nifedipine on L-type Ca(2+) current (I(Ca(L))) were investigated in ventricular cardiomyocytes from rats. Both barnidipine and nifedipine reduced I(Ca(L)) in a concentration and voltage dependent manner; the EC(50) were 80 and 130 nM at a holding potential of -80 mV, respectively, and 18 and 6 nM at -40 mV, respectively. Both drugs induced a leftward shift of the steady-state inactivation curve of I(Ca(L)). Using a twin pulse protocol, the relationships between the amount of block of I(Ca(L)) by either drug, seen during the second pulse, and the length of the first pulse were described by monoexponential functions reflecting onset of block, dependent on drug concentration. The onset of block by barnidipine was three times faster than that by nifedipine. With both drugs, recovery of I(Ca(L)) was 50 times slower than under control conditions and described by monoexponential functions reflecting offset of block (independent of drug concentration). The offset of block with barnidipine was three times slower than that with nifedipine. The time constants of block and unblock of I(Ca(L)) by both drugs were used to calculate binding and unbinding and to predict their effects at two frequencies. It is suggested that barnidipine exhibits a higher affinity to the inactivated Ca(2+) channel state as compared to nifedipine.
Wegener
J W
JW
Pharmakologisches Institut der Universität Mainz, D-55101 Mainz, Germany. Wegener@mail.uni-mainz.de
Meyrer
H
H
Rupp
J
J
Nawrath
H
H
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016276:Ventricular Function
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; C050699:mepirodipine; D009543:Nifedipine