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  • Title: Spermine gates inward-rectifying muscarinic but not ATP-sensitive K+ channels in rabbit atrial myocytes. Intracellular substance-mediated mechanism of inward rectification.
    Author: Yamada M, Kurachi Y.
    Journal: J Biol Chem; 1995 Apr 21; 270(16):9289-94. PubMed ID: 7721849.
    Abstract:
    The effect of spermine, a low molecular mass aliphatic amine with positive charges, on the strongly inwardly rectifying muscarinic K+ (KACh) channel was examined in rabbit atrial myocytes. In inside-out patch membranes, the single channel current-voltage relationship of KACh channels activated by guanosine 5'-3-O-(thio)triphosphate became linear in the absence of intracellular Mg2+. The open probability (Po) of the channels did not show significant voltage dependence under these conditions. Spermine specifically reduced Po of outwardly flowing KACh channel currents without affecting the unitary current amplitude at depolarized potentials, but had no effect on inward KACh currents under hyperpolarization. This voltage dependence of Po of KACh channels in the presence of spermine resembled that normally observed in the whole cell or open cell-attached configurations. Spermine (300 nM to 3 microM) also restored the relaxation of KACh currents which had been lost in the inside-out configuration. The effect of spermine was concentration-dependent with IC50 of approximately 10 nM at +40 mV. The order of potency of polyamines in reducing Po at +40 mV was spermine > or = spermidine > putrescine > ornithine; arginine had no significant effect. Intracellular Mg2+ antagonized the effect of spermine. Neither the single channel conductance nor Po of the ATP-sensitive K+ channel, a weak inward rectifier, was affected by spermine. Because submillimolar concentrations of spermine and spermidine are available in the cytosol of most cells, these substances may be the unidentified intracellular gating factors for strong inward rectifiers such as KACh and IK1 channels.
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