PMID- 2778732
OWN - NLM
STAT- MEDLINE
DCOM- 19891025
LR  - 20190510
IS  - 0022-3751 (Print)
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Linking)
VI  - 408
DP  - 1989 Jan
TI  - Dual effects of intracellular magnesium on muscarinic potassium channel current 
      in single guinea-pig atrial cells.
PG  - 313-32
AB  - 1. The effects of internal Mg2+ ions on the muscarinic acetylcholine (ACh) 
      receptor-mediated K+ currents were investigated in single atrial cells of 
      guinea-pigs, using the whole-cell and inside-out modes of the patch-clamp 
      technique. 2. During cell dialysis in the whole-cell-clamp condition, the 
      depletion of internal Mg2+ increased outward muscarinic K+ currents but decreased 
      inward currents, thereby reducing the inwardly rectifying property of the 
      channels. 3. When inside-out patches were prepared, channel availability was 
      abolished and was reactivated by internal application of guanosine 
      5'-triphosphate (GTP) or its non-hydrolysable analogue, 5'-guanylyl 
      imidodiphosphate (GppNHp), in the presence of Mg2+. GppNHp led to a recovery of 
      the channels also in the nominal absence of Mg2+ (0[Mg2+]i). 4. The activation of 
      single-channel currents by intracellular GTP and Mg2+ was dose-dependent. Both 
      concentration-response curves were fitted by saturation kinetics with Hill 
      coefficients of 1, and the half-maximum doses were 24 +/- 8 microM for GTP and 67 
      +/- 14 microM for Mg2+. The effects of Mg2+ on activation of K+ currents were 
      additive with those of GTP, suggesting the presence of two independent binding 
      sites for GTP and Mg2+. 5. The single-channel conductance became virtually ohmic 
      when measured at nominally zero [Mg2+]i while GppNHp was used to recover the 
      channel activity. Micromolar [Mg2+]i reduced the unitary amplitude of single 
      open-channel currents in a dose- and voltage-dependent manner, showing 
      half-blocking doses of 293 microM at +40 mV and 115 microM at +60 mV. 6. 
      Voltage-dependent kinetics of Mg2+ block were described using equations based on 
      Eyring rate theory (Woodbury, 1971; Hille, 1984), where the coefficient for 
      voltage dependence (delta) was 0.63. 7. Intracellular Mg2+, at a physiological 
      concentration, has a dual action on the muscarinic K+ channel: first Mg2+ 
      activates the channel in the presence of GTP through GTP-binding proteins (G 
      proteins), and secondly it blocks outward currents through the channel, thereby 
      causing the inwardly rectifying property.
FAU - Horie, M
AU  - Horie M
AD  - National Institute for Physiological Sciences, Okazaki, Japan.
FAU - Irisawa, H
AU  - Irisawa H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Potassium Channels)
RN  - 0 (Receptors, Muscarinic)
RN  - 34273-04-6 (Guanylyl Imidodiphosphate)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - I38ZP9992A (Magnesium)
RN  - N9YNS0M02X (Acetylcholine)
SB  - IM
MH  - Acetylcholine/pharmacology
MH  - Animals
MH  - Dose-Response Relationship, Drug
MH  - Electric Conductivity
MH  - Female
MH  - Guanosine Triphosphate/pharmacology
MH  - Guanylyl Imidodiphosphate/pharmacology
MH  - Guinea Pigs
MH  - Heart/*physiology
MH  - Heart Atria
MH  - Magnesium/*physiology
MH  - Male
MH  - Membrane Potentials/drug effects
MH  - Potassium Channels/drug effects/*physiology
MH  - Receptors, Muscarinic/physiology
PMC - PMC1190405
EDAT- 1989/01/01 00:00
MHDA- 1989/01/01 00:01
PMCR- 1989/01/01
CRDT- 1989/01/01 00:00
PHST- 1989/01/01 00:00 [pubmed]
PHST- 1989/01/01 00:01 [medline]
PHST- 1989/01/01 00:00 [entrez]
PHST- 1989/01/01 00:00 [pmc-release]
AID - 10.1113/jphysiol.1989.sp017461 [doi]
PST - ppublish
SO  - J Physiol. 1989 Jan;408:313-32. doi: 10.1113/jphysiol.1989.sp017461.