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DRUGS ACTING ON ION CHANNELS AND OTHER MEMBRANE RECEPTORS - Coggle Diagram
DRUGS ACTING ON ION CHANNELS AND OTHER MEMBRANE RECEPTORS
INTRODUCTION
Receptors are targets for drugs and stimulus
They are all over the body
ION CHANNELS
Cell
inside: K+
NEGATIVELY CHARGED
outside: Na+, Ca2+, Cl-
POSITIVELY CHARGED
Voltage: -70mV
more negative: HiPERPOLARIZED
more positive: DEPOLARIZED
cylinder shape with inner ”gates” that open and close because of physical or chemical stimulus.
types of stimulus:
Ligands and drugs (direct interactions)
Different messengers (indirect interactions)
Voltage changes
They are also extremely selective according to the size and the charge of the ion.
THE IONS BOTH INSIDE AND OUTSIDE THE CELL DO NOT GO ALONE, THEY ARE SURROUNDED BY THEIR SOLVENT LAYER.
TYPES:
Voltage-dependent or voltage-gated ion channels (Na+, K+ and Ca2+ channels)
voltage sensor
S4 segment from the -helix,
one positive charged aminoacid (usually arginine or lysine) per every 3 amino acids
pore:
Segments S5 and S6 from each domain build the channel pore together with the P-loops (also called H5 or P), which is the protein part that connects S5 and S6.
the part of the channel the ions go through, has the shape of a hourglass: two opposite halls and a corridor in the middle.
Ligand-dependent or ligand-gated ion channels (acetylcholine receptor). Acetylcholine nicotinic receptor- sodium channel
The ligand dependent ion channels need to be linked to a ligand to be able to open and so to facilitate the flow of ions through them
the ligand:
acetylcholine molecule
the positive charge of the nitrogen is distributed in the 3 methyl groups
the distance between the N and the ester must be kept
the trimethylic chain or the acid chain can ́t be longer
there must be, at least, 2 metyhl groups on the nitrogen
the receptor:
acetylcholine nicotinic receptor
The part of the nicotinic receptor that interacts with the acetylcholine
histidine
aspartic acid
glutamic acid
tyrosine
The part associated to the sodium channel
The acetylcholine interaction sites are on the alpha subunits and the centre of the cylinder is the ionic channel.
OTHER RELATED RECEPTOR
Receptors with intrinsic enzymatic activity (receptors with tyrosine-kinase activity)
3 domains: extracellular, transmembrane, intracellular (tyrosine-kinase protein)
Metabotropic receptors (G-coupled receptors)
affinity for guanine nucleotides
G proteins can be coupled to other proteins with catalytic activity or to ion channels.
The signal transmission is carried out through the cytoplasm, thanks to:
regulating enzymes from G-proteins: Indirect pathway
the binding of G-proteins with ion channels: Direct pathway
GENERAL FACTS TO CONSIDER
healthy conditions, receptors are metabolized are regenerated in hours or days.
pathological conditions or under long pharmacological treatments cells can suffer:
desensitization: when the response to certain drugs is weaker than expected
hypersensitization: when the response to certain drugs is stronger than expected