Inhibition by external Cd2+ of Na/Ca exchange and L-type Ca channel in rabbit ventricular myocytes.
We investigated the effect of external Cd2+ on the Na/Ca exchange and the L-type Ca channel current (ICa,L) in whole cell patch-clamped rabbit ventricular myocytes at 36 degrees C. After the interfering ion channels and the Na/K pump were blocked, the exchange current was measured as the membrane current that was inhibited by 5 mM nickel. External Cd2+ inhibited Na/Ca exchange with a dissociation constant (KD) of 320.6 +/- 12.4 microM and a Hill coefficient of 1.5 +/- 0.09 (n = 13 cells) and ICa,L with a KD of 2.14 +/- 0.15 microM and a Hill coefficient of 0.74 +/- 0.03 (n = 11 cells). We observed some overlap in the Cd2+ concentration that blocked each mechanism. Cd2+ (100-500 microM) is used commonly to block ICa,L completely. However, 100 microM Cd2+ also inhibits 20% of the Na/Ca exchange activity, whereas 500 microM Cd2+ inhibits 60%.
Hobai
I A
IA
Department of Physiology, School of Medical Sciences, University of Bristol, United Kingdom.
Bates
J A
JA
Howarth
F C
FC
Levi
A J
AJ
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002104:Cadmium / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000502:physiology*; D004553:Electric Conductivity; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D008564:Membrane Potentials; D009206:Myocardium / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D010455:Peptides; D002104:Cadmium; C066745:exchanger inhibitory peptide; D012964:Sodium; D002118:Calcium