Showing papers by "Thomas Baukrowitz published in 2000"

Polyamines as gating molecules of inward-rectifier K+ channels.

Abstract: Inward-rectifier potassium (Kir) channels comprise a superfamily of potassium (K+) channels with unique structural and functional properties. Expressed in virtually all types of cells they are responsible for setting the resting membrane potential, controlling the excitation threshold and secreting K+ ions. All Kir channels present an inwardly rectifying current–voltage relation, meaning that at any given driving force the inward flow of K+ ions exceeds the outward flow for the opposite driving force. This inward-rectification is due to a voltage-dependent block of the channel pore by intracellular polyamines and magnesium. The present molecular–biophysical understanding of inward-rectification and its physiological consequences is the topic of this review. In addition to polyamines, Kir channels are gated by intracellular protons, G-proteins, ATP and phospholipids depending on the respective Kir subfamily as detailed in the following review articles.

KATP channels gated by intracellular nucleotides and phospholipids

Abstract: The KATP channel is a heterooctamer composed of two different subunits, four inwardly rectifying K+ channel subunits, either Kir6. 1 or Kir6.2, and four sulfonylurea receptors (SUR), which belong to the family of ABC transporters. This unusual molecular architecture is related to the complex gating behaviour of these channels. Intracellular ATP inhibits KATP channels by binding to the Kir6.x subunits, whereas Mg-ADP increases channel activity by a hydrolysis reaction at the SUR. This ATP/ADP dependence allows KATP channels to link metabolism to excitability, which is important for many physiological functions, such as insulin secretion and cell protection during periods of ischemic stress. Recent work has uncovered a new class of regulatory molecules for KATP channel gating. Membrane phospholipids such as phosphoinositol 4, 5-bisphosphate and phosphatidylinositiol 4-monophosphate were found to interact with KATP channels resulting in increased open probability and markedly reduced ATP sensitivity. The membrane concentration of these phospholipids is regulated by a set of enzymes comprising phospholipases, phospholipid phosphatases and phospholipid kinases providing a possible mechanism for control of cell excitability through signal transduction pathways that modulate activity of these enzymes. This review discusses the mechanisms and molecular determinants that underlie gating of KATP channel by nucleotides and phospholipids and their physiological implications.

Controls Fast Inhibitory Synaptic Transmission at Auditory Outer Hair Cells

Abstract: Summary 10 mM (Xia et al., 1998; Hirschberg et al., 1999; Keen etal., 1999). Fast inhibitory synaptic transmission in the central Consequently, the transduction cascade deducednervous system is mediated by ionotropic GABA or from application of acetylcholine to isolated hair cells glycine receptors. Auditory outer hair cells present a (Figure1A)predictstheOHCstobehyperpolarizeduponsynaptic stimulation for as long as [Ca 2 1 ] unique inhibitory synapse that uses a Ca 2 1 -permeable i is sufficiently excitatory acetylcholine receptor to activate a hyper- high to activate SK channels. However, hyperpolarizing polarizing potassium current mediated by small con- K 1 currents evoked by presynaptic activity have not yet ductance calcium-activated potassium (SK) channels. been measured directly. It is shown here that unitary inhibitory postsynaptic Here we investigated the inhibitory synaptic transmis- currentsatthissynapsearemediatedbySK2channels sion at OHCs by monitoring the coupling between the