Measuring the length of the pore of the sheep cardiac sarcoplasmic reticulum calcium-release channel using related trimethylammonium ions as molecular calipers.
After incorporation of purified sheep cardiac Ca(2+)-release channels into planar phospholipid bilayers, we have investigated the blocking effects of a series of monovalent (CH3-(CH2)n-1-N+(CH3)3) and divalent ((CH3)3N(+)-(CH2)n-N+(CH3)3) trimethylammonium derivatives under voltage clamp conditions. All the compounds tested produce voltage-dependent block from the cytoplasmic face of the channel. With divalent (Qn) derivatives the effective valence of block decreases with increasing chain length, reaching a plateau with a chain length of n > or = 7. No decline in effective valence is observed with the monovalent (Un) derivatives. A plausible interpretation of this phenomena suggests that for the 90% of the voltage drop measured, the increase in length following the addition of a CH2 in the chain spans 12.7% of the electrical field. Extrapolating this distance to include the remaining 10% suggests that the applied holding potential falls over a total distance of 10.4 A. In addition, at high positive holding potentials there is evidence for permeation of the trimethylammonium ions and a valency specific relief of block.
Tinker
A
A
Department of Cardiac Medicine, National Heart and Lung Institute, University of London, United Kingdom.
Williams
A J
AJ
D000818:Animals; D055592:Biophysical Phenomena; D001703:Biophysics; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000494:pharmacology; D015220:Calcium Channels / Q000737:chemistry* / Q000302:isolation & purification; D004563:Electrochemistry; D066298:In Vitro Techniques; D007473:Ion Channels / Q000737:chemistry; D008051:Lipid Bilayers; D008564:Membrane Potentials; D015394:Molecular Structure; D009124:Muscle Proteins / Q000737:chemistry* / Q000302:isolation & purification; D009206:Myocardium / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel; D012519:Sarcoplasmic Reticulum / Q000737:chemistry*; D012756:Sheep
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007473:Ion Channels; D008051:Lipid Bilayers; D009124:Muscle Proteins; D000644:Quaternary Ammonium Compounds; D019837:Ryanodine Receptor Calcium Release Channel