5. cell communication

• Forms of Intercellular Signalling:

  • Contact-Dependent Signaling involves a signaling molecule bound to the cell surface, seen in interactions during development and the immune response.
  • Paracrine Signaling includes the secretion of signal molecules that diffuse short distances to exert local effects.
  • Synaptic Signaling is specific to neurons, where neurotransmitters are released from the presynaptic cell and act on receptors of the postsynaptic cell.
  • Endocrine Signaling involves the secretion of hormones into the bloodstream by endocrine glands, affecting distant target cells
• Cell-Surface Receptors:

  • 3 major classes: Ion-Channel-Linked Receptors, G-Protein-Coupled Receptors, and Enzyme-Linked Receptors.
  • These receptors transform extracellular binding events into intracellular signals through "signal transduction"
• Ion-Channel-Linked Receptors (Ionotropic Receptors):

  • Function as both receptors and ion channels.
  • Ligand binding causes a conformational change opening the ion channel.
  • Examples include glutamate receptors and acetylcholine receptors
• 1. Protein-Coupled Receptors (Metabotropic Receptors):

  • Activate intracellular signaling pathways through interaction with G-proteins.
  • Ligand binding activates G-proteins, modulating intracellular enzymes or ion channels.
  • Involved in various physiological processes and targeted by pharmaceutical drugs
• Enzyme-Linked Receptors:

  • Have an intracellular enzymatic domain activated upon ligand binding.
  • Activation involves autophosphorylation, initiating downstream signaling cascades.
  • Examples include growth factor receptors like the epidermal growth factor receptor (EGFR)
• Ion-Channel-Linked (Ionotropic) Receptors:

  • Composed of subunits with multiple transmembrane segments forming a functional receptor complex.
  • Localized at specific sites within the plasma membrane, particularly at synapses.
  • Reversibly bind neurotransmitters, leading to a conformational change and ion channel opening
• Neurotransmitters:

  • Produced in the cytosol of neurons, stored in synaptic vesicles.
  • Synthesized in the presynaptic terminal and released upon stimulation.
  • Include amino acids, monoamines, and neuropeptides like glutamate and acetylcholine
• Signalling at a Chemical Synapse:

  • The synapse is a specialized region between two adjacent cells, involving presynaptic and postsynaptic neurons.
  • Neurotransmitters are released into the synaptic cleft, binding to postsynaptic receptors.
  • Excitatory synapses lead to depolarization, while inhibitory synapses cause hyperpolarization
• Excitatory or Inhibitory Chemical Synapses:

  • Excitatory synapses result in a net gain of positive charge, enhancing cell excitability.
  • Inhibitory synapses lead to a net loss of positive charge, reducing cell excitability.
  • Examples of neurotransmitters: glutamate and acetylcholine for excitatory synapses, GABA and glycine for inhibitory synapses
• The Neuromuscular Junction:

  • Represents the point of synaptic contact between the presynaptic motor neuron and the postsynaptic muscle fiber
• The neuromuscular junction is the point of synaptic contact between the presynaptic motor neuron and the postsynaptic muscle cell
• Chemical signaling at the neuromuscular junction initiates muscle contraction
• Components of the neuromuscular junction include the presynaptic motor neuron terminal and the postsynaptic muscle cell membrane
• Acetylcholine (ACh) is the neurotransmitter responsible for transmitting signals from the motor neuron to the muscle cell at the neuromuscular junction
• Ionotropic receptors for ACh at the neuromuscular junction are nicotinic acetylcholine receptors (nAChRs), which are ligand-gated ion channels
• When ACh binds to nAChRs on the muscle cell membrane, positively charged ions like sodium (Na⁺) flow into the muscle cell, depolarizing the membrane and triggering muscle contraction
• The neuromuscular junction plays a crucial role in controlling voluntary muscle movement
• Dysfunction at the neuromuscular junction can lead to neuromuscular disorders like myasthenia gravis, where autoantibodies target and impair nAChRs, causing muscle weakness and fatigue
• Acetylcholine receptors (AChRs) are composed of five subunits arranged in a ring formation around a central pore
• The alpha subunits of AChRs contain the binding sites for acetylcholine, inducing a conformational change in the receptor upon binding
• The central pore of AChRs allows the movement of positively charged ions like sodium (Na⁺) and potassium (K⁺)
• Near the central pore of AChRs, negatively charged amino acid residues attract positively charged ions, promoting their passage through the channel
• Binding of ACh to the alpha subunits of AChRs induces a conformational change, leading to the opening of the gate and an increase in ion permeability
• Two molecules of acetylcholine (ACh) must bind to the alpha subunits of AChRs for the channel to open, allowing both sodium (Na⁺) and potassium (K⁺) ions to flow through
• Sodium and potassium ions move in opposite directions due to differences in their concentration gradients and electrochemical potentials
• The net gain of positive charge inside the cell is primarily due to the stronger inward driving force of sodium ions compared to potassium ions
• The membrane potential at the resting state is approximately -70 millivolts, with equilibrium potentials for sodium and potassium ions at +60 mV and -80 mV, respectively
• The large difference between the resting membrane potential and the equilibrium potential for sodium ions results in sodium ions dominating the movement upon AChR activation, leading to membrane depolarization and increased excitability
• AChRs are excitatory receptors, and synapses containing these receptors are termed excitatory synapses due to the net increase in positive charge and membrane depolarization upon activation
• Glutamate receptors, the main excitatory neurotransmitter receptors in the mammalian central nervous system, have a structure and function similar to ACh receptors
• Both non-NMDA and NMDA glutamate receptors require the presence of glutamate for activation, leading to changes in membrane potential upon receptor activation
• NMDA receptors have unique properties such as requiring glycine for activation, permeability to calcium ions, and magnesium blockade that is relieved upon membrane depolarization
• The magnesium blockade is relieved when the membrane is depolarized
• Depolarization causes magnesium ions to be displaced from the pore, allowing ions like sodium, potassium, and calcium to flow through the channel
• Glutamate receptors play a major role in learning and memory
• Glutamate receptors are located in mammalian hippocampal neurons
• Short bursts of activity from presynaptic neurons can have long-lasting effects on the glutamate sensitivity of postsynaptic receptors
• This process, known as "long-term potentiation," underlies learning and can last hours, days, or weeks
• In long-term potentiation (LTP), the resting state involves both pre- and postsynaptic cells being at rest and polarized
• Glutamate release occurs when there is a short burst of activity in the presynaptic neuron, leading to glutamate binding to NMDA and non-NMDA receptors on the postsynaptic membrane