Intracellular nucleotides and polyamines inhibit the Ca2+-activated cation channel TRPM4b

Pflugers Arch. 2004 Apr;448(1):70-5. doi: 10.1007/s00424-003-1221-x. Epub 2004 Jan 31.

Abstract

TRPM4b (in contrast to the short splice variant TRPM4a) is a Ca(2+)-activated but Ca(2+)-impermeable cation channel. We have studied TRPM4 currents in inside-out patches. Supramicromolar Ca(2+) concentrations applied at the inner side, [Ca(2+)](i), activated TRPM4 with an EC(50) value of 0.37 mM, a value that is much higher than that of whole-cell currents. Current amplitudes decreased above 1 mM [Ca(2+)](i), (IC(50) 9.3 mM). Sr(2+) but not Ba(2+)could partially substitute for Ca(2+). ATP, ADP, AMP and AMP-PNP all quickly and reversibly inhibited TRPM4 with IC(50) values between 2 and 19 microM (at +100 mV). Adenosine also blocked TRPM4 at 630 microM. The block at high ATP concentrations was incomplete and was not affected by the presence of free Mg(2+). ADP induced the most sensitive block with an IC(50) of 2.2 microM. For inhibition of TRPM4 by free ATP(4-), an IC(50) value of 1.7+/-0.3 microM was calculated. GTP, UTP and CTP at concentrations up to 1 mM did not induce a similar block. Spermine blocked TRPM4 currents with an IC(50) of 61 microM. In conclusion, TRPM4 is a channel that can be effectively modulated by intracellular nucleotides and polyamines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine Nucleotides / pharmacology*
  • Calcium / pharmacology
  • Calcium Channels / metabolism
  • Cation Transport Proteins / antagonists & inhibitors*
  • Cation Transport Proteins / metabolism
  • Cell Line
  • Cells, Cultured
  • Humans
  • Inhibitory Concentration 50
  • Kidney / embryology
  • Kidney / metabolism
  • Patch-Clamp Techniques
  • Spermine / pharmacology*
  • TRPM Cation Channels

Substances

  • Adenine Nucleotides
  • Calcium Channels
  • Cation Transport Proteins
  • TRPM Cation Channels
  • TRPM4 protein, human
  • Spermine
  • Calcium