Novel blockade of Ca2+ current by quinacrine in smooth muscle cells of the guinea pig.
Effects of quinacrine on voltage-dependent Ca2+ channel current (ICa) were examined using whole cell voltage clamp in single smooth muscle cells isolated from vas deferens and urinary bladder and single cardiac myocytes from ventricle of the guinea pig. When ICa was elicited by depolarization from a holding potential of -60 to 0 mV for 150 msec every 15 sec in vas deferens myocytes, external application of quinacrine reduced the amplitude of ICa in a concentration-dependent manner in a range of 0.1 approximately 30 microM, and the IC50 of quinacrine was 1.3 microM. The block was at least partly removed by washout. The block of ICa by 1 microM quinacrine in vas deferens myocytes greatly depended upon the activation potentials but only slightly on the holding potentials. Use-dependent development of the block was also observed. Addition of 300 microM quinacrine to the pipette-filling solution did not significantly affect ICa. The IC50 of quinacrine for ICa block in urinary bladder myocytes was 1.1 microM and comparable to that in vas deferens. On the other hand, IC50 for the block of ICa elicited by depolarization from -45 to 0 mV in cardiac ventricular myocytes was 5.6 microM. It is concluded that quinacrine is a potent blocker of L-type Ca2+ channels in two types of smooth muscle myocytes and that the potency appeared to be approximately five times higher than that in cardiac myocytes. The action of quinacrine may be due to the direct block of Ca2+ channels from outside of the cell membrane.
Nagano
N
N
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Nagoya City University, Japan.
Imaizumi
Y
Y
Watanabe
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011796:Quinacrine / Q000494:pharmacology*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism
D002121:Calcium Channel Blockers; D011796:Quinacrine; D002118:Calcium