The fibroblast intermediate conductance K(Ca) channel, FIK, as a prototype for the cell growth regulatory function of the IK channel family.
The fibroblast intermediate conductance, calcium-activated potassium channel (FIK) is proposed here as a functional prototype for other IK channels which to date have undefined physiologic actions. FIK pharmacology in the 10T1/2-MRF4 myogenic fibroblast cell line was determined: to define the relationship of FIK to other IKs; to confirm a physiologic role for FIK; and, thus develop a hypothesis about IK channel family function. Whole cell patch-clamp electrophysiology was used to determine K(0.5) values for FIK block by the structurally related peptides charybdotoxin (ChTX) (7 nm) and iberiotoxin (IbTX) (536 nm), and a new unrelated FIK inhibitor, Stichodactyla toxin (StK) (85 nm). Peptide pharmacology for FIK was consistent with that of recently cloned IKs. ChTX and StK inhibited bFGF stimulated 10T1/2-MRF4 cell proliferation with dose-dependencies consistent with their FIK blocking actions. ChTX, StK, and IbTX also evoked MRF4-dependent transcription as measured by muscle acetylcholine receptor channel functional expression; but they did not evoke subsequent multinucleated fiber formation or myosin heavy chain expression, suggesting a role for FIK in early, rather than late, myogenic events. Thus despite structural differences, ChTX, IbTX, and StK have common effects on cell growth and differentiation reflecting their common FIK blocking action. We suggest that a major function of the IK channel family is to regulate cell growth.
Peña
T L
TL
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Rane
S G
SG
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D018999:Charybdotoxin / Q000494:pharmacology; D003064:Cnidarian Venoms / Q000494:pharmacology; D005347:Fibroblasts / Q000502:physiology*; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D009498:Neurotoxins / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D024681:Potassium Channels, Calcium-Activated; D051381:Rats; D015398:Signal Transduction; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014118:Toxins, Biological / Q000494:pharmacology
D003064:Cnidarian Venoms; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D009498:Neurotoxins; D010455:Peptides; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014118:Toxins, Biological; D018999:Charybdotoxin; C059713:neurotoxin I, Stichodactyla helianthus; C064719:iberiotoxin