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 Ca2+-release channels in to planar phospholipid bilayers, we have investigated the blocking eff ects of a series of monovalent (CH3-(CH2)(n-1)-N+C(CH3)(3)) and divale nt ((CH3N+-(CH2)(n)-N+(CH3)(3)) trimethylammonium derivatives under vo ltage clamp conditions. All the compounds tested produce voltage-depen dent block from the cytoplasmic face of the channel. With divalent (On ) derivatives the effective valence of block decreases with increasing chain length, reaching a plateau with a chain length of n greater tha n or equal to 7. No decline in effective valence is observed with the monovalent (Un) derivatives. A plausible interpretation of this phenom ena suggests that for the 90% of the voltage drop measured, the increa se in length following the addition of a CH2 in the chain spans 12.7% of the electrical field. Extrapolating this distance to include the re maining 10% suggests that the applied holding potential falls over a t otal distance of 10.4 Angstrom. In addition, at high positive holding potentials there is evidence for permeation of the trimethylammonium i ons and a valency specific relief of block.