CLOSURE OF POTASSIUM M-CHANNELS BY MUSCARINIC ACETYLCHOLINE-RECEPTOR STIMULANTS REQUIRES A DIFFUSIBLE MESSENGER

The M-current (I(K(M))) is a slow voltage-gated K+ current which can be inhibited by muscarinic acetylcholine-receptor (mAChR) agonists. In the present experiments we have tested whether this inhibition results from a local (membrane-delimited) interaction between the receptor and adjacent channels, or whether channel closure is mediated by a diffusible messenger. To do this, single K(M)+-channel currents were recorded from membrane patches in dissociated rat superior cervical sympathetic neurons by using cell-attached patch electrodes. Channel activity was inhibited when muscarine was applied to the cell membrane outside the patch but persisted when channels were exposed to muscarine added to the pipette solution. We conclude that a diffusible molecule (or molecules) is (are) required to induce intra-patch patch channel closure following activation of extra-patch receptors.