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Regulation of a mammalian Shaker ‐related potassium channel, h Kv1.5, by extracellular potassium and pH
Author(s) -
Jäger Heike,
Grissmer Stephan
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)02396-6
Subject(s) - shaker , chemistry , histidine , protonation , extracellular , potassium channel , potassium , biophysics , patch clamp , stereochemistry , amino acid , biochemistry , ion , biology , organic chemistry , physics , receptor , quantum mechanics , vibration
Using the whole‐cell recording mode of the patch‐clamp technique we studied the effects of removal of extracellular potassium, [K + ] o , on a mammalian Shaker ‐related K + channel, h Kv1.5. In the absence of [K + ] o , current through h Kv1.5 was similar to currents obtained in the presence of 4.5 mM [K + ] o . This observation was not expected as earlier results had suggested that either positively charged residues or the presence of a nitrogen‐containing residue at the external TEA + binding site (R487 in h Kv1.5) caused current loss upon removal of [K + ] o . However, the current loss in h Kv1.5 was observed when the extracellular pH, pH o , was reduced from 7.4 to 6.0, a behavior similar to that observed previously for current through m Kv1.3 with a histidine at the equivalent position (H404). These observations suggested that the charge at R487 in h Kv1.5 channels was influenced by other amino acids in the vicinity. Replacement of a histidine at position 463 in h Kv1.5 by glycine confirmed this hypothesis making this H463G mutant channel sensitive to removal of [K + ] o even at pH o 7.4. We conclude that the protonation of H463 at pH 7.4 might induce a p K a shift of R487 that influences the effective charge at this position leading to a not fully protonated arginine. Furthermore, we assume that the charge at position 487 in h Kv1.5 can directly or indirectly disturb the occupation of a K + binding site within the channel pore possibly by electrostatic interaction. This in turn might interfere with the concerted transition of K + ions resulting in a loss of K + conduction.