Effects of NS 1608 on MaxiK channels in smooth muscle cells from urinary bladder

Summary
Using the patch-clamp technique, we have characterized membrane currents in single detrusor smooth muscle cells from rat and human urinary bladder.  From the voltage- and Ca²⁺-dependence of the current as well as the single channel conductance we conclude that rat and human urinary bladder smooth muscle cells express MaxiK channels.  In smooth muscle cells from rat urinary bladder we tested the action of NS1608 on current through these MaxiK channels.  Application of 10 mM NS1608 increased the amplitude of the current and this increase could be explained by a shift in the activation voltage of the MaxiK channels ~100 mV towards more negative potentials.  Charybdotoxin as well as paxilline, well known blockers of MaxiK channels, were able to reduce current through MaxiK channels in our cell preparation.  In addition, application of 10 mM NS1608 hyperpolarized the membrane potential of the investigated cells.  This hyperpolarization could be antagonized by the application of paxilline.  We conclude that application of NS1608 results in the opening of MaxiK channels under physiological conditions that leads to a hyperpolarization of the cells.  This hyperpolarization in turn could relax urinary bladder smooth muscle cells.  MaxiK channels in these cells could therefore play a role in directly controlling muscle tone by regulating the membrane potential.  This opens up the possibility of MaxiK channels being targets for the treatment of urge incontinence.
Published as:
Siemer C, Bushfield M, Newgreen D, Grissmer S.  2000.  Effects of NS1608 on MaxiK channels in smooth muscle cells from urinary bladder. Journal of Membrane Biology 173:57-66.
 

MaxiK channels:  Molecular structure, function, and tissue distribution

Summary
MaxiK channels are expressed in a variety of tissues, exist in several alternative splice variants, and may or may not associate with a beta-subunit.  Through those combinations of splice variants with or without the beta-subunit, specific MaxiK channels with different physiological functions and pharmacology may exist in each tissue.  This opens up the possibility of MaxiK channels being attractive and tissue specific targets for therapeutic intervention for a variety of applications including asthma and hypertension.
Published as:
Siemer C, Grissmer S.  1999.  MaxiK channels:  Molecular structure, function, and tissue distribution. Perspectives in Drug Discovery and Design 15/16:155-165.