A Large Entrance To the Inner Cavity of BK Channels Is Required For Their Large Conductance

摘要: of a dissertation at the University Miami. Dissertation supervised by Professor Karl L. Magleby No. pages in text. (69) Large conductance voltage and Ca activated K (BK) channels control electrical excitability many cell types. BK have largest (~250 pS) all selective channels. To explore whether large entrance to inner cavity is required for their conductance, I examined if changing size alters single-channel current amplitude. Previous studies suggest that residues E321/E324 are located cavity. test positions 321/324 accessible intracellular ions, compared outward before after attaching thiol reagents E321C/E324C. Attachment MBB MTSET altered currents, indicating conduction pathway. Decreasing substituting with larger side chains, such as tyrosine tryptophan, decreased whereas increasing had little effect on conductance. Increasing [K]i from 0.15 2.5 M negated differences associated chain volume. Substitutions less inward currents. Plots vs. substituted volume could be approximated simple model pathway described two resistors series, R1 R2. R2 variable resistor, resistance proportional inverse not occupied chains. fixed resistor arising other parts including selectivity filter. Fitting experimental observations indicated R1+R2 ~5.4 GΩ glycine substitution, an R1/R2 ratio ~17, effective radius length ~9.0 5.4 A, respectively. The water were taken into account. Taken together, above needed channels, my study shows decreasing decreases