Lecture 4 - Drugs and calcium signalling

• Concentration of intracellular Ca2+

  Determined by the balance of Ca2+ entry, extrusion, and exchange between cytosol, ER/SR, and mitochondria
• Calcium regulation of mediator release

  1. Exocytosis

  2. Diffusible mediators via enzyme activation

  3. Promotion of neuronal excitability and plasticity

  4. Stabilization of dendritic spines
• Intracellular calcium regulation

  1. Ca2+ entry

  2. Ca2+ extrusion

  3. Ca2+ exchange
• Calcium role in balancing metabolism and apoptosis

  Through ER-mitochondrial signaling, crucial for determining normal cell function or programmed cell death
• Calcium role in stabilizing dendritic spines


  Localized changes in cytosolic calcium levels contribute to the stabilization of dendritic spines, maintaining synaptic connections and integrating incoming signals
• Calcium storage

  Endoplasmic reticulum (ER) and sarcoplasmic reticulum (SR) store calcium, released in response to stimuli
• Increased intracellular calcium

  Activates enzymes responsible for synthesis of non-stored mediators like prostanoids and nitric oxide, allowing their release
• Calcium entry


  Occurs through channels and Na+/Ca2+ exchange
• Processes involving calcium regulation

  • Synaptic plasticity
  • Excitability
  • Exocytosis
  • Motility
  • Contraction
  • Differentiation
  • Mitosis
  • Meiosis
  • Apoptosis
• Calcium ions


  • Affect various aspects of cell function by binding to proteins such as calmodulin, which then regulate the function of other proteins
• Intracellular calcium concentration increases

  Causes Ca2+-mediated interaction between proteins of synaptic vesicle and plasma membrane, leading to exocytosis
• Calcium role in promoting neuronal excitability and plasticity


  Required for short- and long-term plasticity, phosphorylation of AMPA receptors, insertion of more AMPA receptors, and structural changes in dendritic spines
• Aberrant calcium dynamics

  Excessive or insufficient levels can disrupt normal cell cycle and apoptosis regulation, contributing to cancer development and progression
• Calcium regulation of cell cycle

  Controls protein kinase C (PKC) and calmodulin, regulating expression and activity of cyclin-dependent kinases (cdks) to progress cells into the S phase