Intracellular calcium directly inhibits potassium M channels in excised membrane patches from rat sympathetic neurons.
Complex effects of altering intracellular [Ca2+] on M-type K+ currents have previously been reported using whole-cell current recording. To study the direct effect of Ca2+ on M-channel activity, we have applied Ca2+ to the inside face of membrane patches excised from rat superior cervical sympathetic ganglion cells. Ca2+ rapidly and reversibly inhibited M-channel activity in 28/44 patches by up to 87%, with a mean IC50 of 100 nM. This effect persisted in the absence of ATP, implying that it was not due to phosphorylation/dephosphorylation. A similar effect was observed in 13/13 cell-attached patches when cells were transiently "Ca(2+)-loaded" by adding 2 mM Ca2+ to a 25 mM K+ solution bathing the extrapatch cell membrane. These observations provide new evidence that Ca2+ can directly inhibit M channels, so supporting the view that Ca2+ might mediate M current inhibition following muscarinic receptor activation.
Selyanko
A A
AA
Department of Pharmacology, University College London, United Kingdom.
Brown
D A
DA
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D007424:Intracellular Fluid / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011499:Protein Processing, Post-Translational; D051381:Rats; D015290:Second Messenger Systems; D017783:Superior Cervical Ganglion / Q000166:cytology
D015221:Potassium Channels; D000255:Adenosine Triphosphate; D011188:Potassium; D002118:Calcium