The effect of pH on the block by L-cis-diltiazem and amiloride of the cyclic GMP-activated conductance of salamander rods.
Block by L-cis-diltiazem and amiloride of the cyclic GMP-activated conductance was studied in inside-out patches excised from the salamander rod outer segment. When cytoplasmic pH was varied, the steady-state level of block by L-cis-diltiazem changed in the way that would be predicted if it were the protonated ammonium group that is responsible for effecting block. This is in contrast to the recent results of Haynes (J. gen. Physiol. 100, 783 (1992)) in catfish cones, where no such change was seen. Amiloride was found to block the conductance with a similar voltage dependence to that of L-cis-diltiazem. The dependence of amiloride block on cytoplasmic pH was found to be shifted relative to that of L-cis-diltiazem, consistent with the 1 pH-unit higher pKa value of amiloride and the idea that it is only the charged form of amiloride which can effect block. This suggests that the results seen with L-cis-diltiazem were indeed due to changes in the proportion of blocker in the protonated form, and not to effects of protons on the channel.
McLatchie
L M
LM
Physiological Laboratory, University of Cambridge, U.K.
Matthews
H R
HR
D000557:Ambystoma; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism*; D003593:Cytoplasm / Q000502:physiology; D004110:Diltiazem / Q000494:pharmacology*; D004553:Electric Conductivity / Q000187:drug effects / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D012374:Rod Cell Outer Segment / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D000584:Amiloride; D004110:Diltiazem; D006152:Cyclic GMP