Effects of NS1608 on MaxiK channels in smooth muscle cells from urinary bladder.
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 Ca(2+)-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 microm NS1608 increased the amplitude of the current and this increase could be explained by a shift in the activation voltage of the MaxiK channels approximately 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 microm 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.
Siemer
C
C
Department of Applied Physiology, University of Ulm, Albert-Einstein-Allee 11, 89081 Ulm, Germany.
Bushfield
M
M
Newgreen
D
D
Grissmer
S
S
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D018999:Charybdotoxin / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000494:pharmacology; D006801:Humans; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051419:Paxillin; D010671:Phenylurea Compounds / Q000494:pharmacology*; D010750:Phosphoproteins / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D051381:Rats; D001743:Urinary Bladder / Q000502:physiology*
D003598:Cytoskeletal Proteins; C494841:KCNMA1 protein, human; C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; C496061:PXN protein, human; D051419:Paxillin; D010671:Phenylurea Compounds; D010750:Phosphoproteins; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; C496063:Pxn protein, rat; D018999:Charybdotoxin; C103727:NS 1608