Hpm. Vijverberg et al., DIFFERENTIAL-EFFECTS OF HEAVY-METAL IONS ON CA2-DEPENDENT K+ CHANNELS(), Cellular and molecular neurobiology, 14(6), 1994, pp. 841-857
1. The ability of various divalent metal ions to substitute for Ca2+ i
n activating distinct types of Ca2+-dependent K+ [K+(Ca2+)] channels h
as been investigated in excised, inside-out membrane patches of human
erthrocytes and of clonal N1E-115 mouse neuroblastoma cells using the
patch clamp technique. The effects of the various metal ions have been
compared and related to the effects of Ca2+. 2. At concentrations bet
ween 1 and 100 mu M Pb2+, Cd2+ and Co2+ activate intermediate conducta
nce K+(Ca2+) channels in erythrocytes and large conductance K+(Ca2+) c
hannels in neuroblastoma cells. Pb2+ and Co2+, but not Cd2+, activate
small conductance K+(Ca2+) channels in neuroblastoma cells. Mg2+ and F
e2+ do not activate any of the K+(Ca2+) channels. 3. Rank orders of th
e potencies for K+(Ca2+) activation are Pb2+, Cd2+ > Ca2+, Co2+ >> Mg2
+, Fe2+ for the intermediate erythrocyte K+(Ca2+) channel, and Pb2+, C
d2+ > Ca2+ > Co2+ >> Mg2+, Fe2+ for the small, and Pb2+ > Ca2+ > Co2>> Cd2+, Mg2+, Fe2+ for the large K+(Ca2+) channel in neuroblastoma ce
lls. 4. At high concentrations Pb2+, Cd2+, and Co2+ block K+(Ca2+) cha
nnels in erythrocytes by reducing the opening frequency of the channel
s and by reducing the single channel amplitude. The potency orders of
the two blocking effects are Pb2+ > Cd2+, Co2+ >> Ca2+, and Cd2+ > Pb2
+, Co2+, Ca2+, respectively, and are distinct from the potency orders
for activation. 5. It is concluded that the different subtypes of K+(C
a2+) channels contain distinct regulatory sites involved in metal ion
binding and channel opening. The K+(Ca2+) channel in erythrocytes appe
ars to contain additional metal ion interaction sites involved in chan
nel block.