Regulation of K+ channels underlying the slow afterhyperpolarization in enteric afterhyperpolarization-generating myenteric neurons: role of calcium and phosphorylation.
1. Myenteric afterhyperpolarization-generating myenteric (AH) neurons serve as intrinsic primary afferent neurons of the enteric nervous system and generate prolonged or slow afterhyperpolarizing potentials (slow AHP). The slow AHP is generated by an increase in a Ca2+-activated K+ conductance (gK-Ca) and is inhibited by enteric neurotransmitters leading to increased excitability. 2. Using cell-attached patch-clamp recordings from AH neurons, we have shown that K+ channels with an intermediate unitary conductance (IK channels) open following action potential firing. 3. In excised patches from AH neurons, we have identified an IK-like channel that can be activated by submicromolar levels of cytoplasmic Ca2+ and is not voltage dependent. 4. Application of the catalytic subunit of cAMP-dependent protein kinase to the cytoplasmic surface of inside-out patches inhibits the opening of IK-like channels previously activated by Ca2+. 5. The IK-like channels are resistant to external tetraethylammonium (5 mmol/L) and apamin (0.3-1 micro mol/L), but are inhibited by clotrimazole (10 micro mol/L). 6. Our present data support the idea that an increase in the open probability of IK-like channels in AH neurons following an increase in cytoplasmic [Ca2+] is responsible for the slow AHP and their opening is modulated by kinases.
Vogalis
Fivos
F
Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Victoria, Australia. fivos@unimelb.edu.au
Harvey
John R
JR
Neylon
Craig B
CB
Furness
John B
JB
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology*; D017615:Enteric Nervous System / Q000378:metabolism / Q000502:physiology; D006801:Humans; D009197:Myenteric Plexus / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D015221:Potassium Channels / Q000378:metabolism* / Q000502:physiology
D015221:Potassium Channels; D002118:Calcium