Transduction and Receptors 1

Photoreceptors: Cones

Cones are the primary photoreceptors in daylight conditions because rods are saturated.

  • Resting membrane potential: Around −40-40 to −50-50 mV, more depolarized than typical neurons (−65-65 to −70-70 mV). This allows signaling in both directions (hyperpolarization and depolarization).
  • Neurotransmitter: Glutamate, constantly released in the dark, stimulating the postsynaptic partner.
  • Light exposure: Causes sodium channels in the outer segment to close, leading to hyperpolarization and reduced glutamate release.
  • Darkness: Sodium channels open, causing depolarization and increased glutamate release.
  • Temporal resolution: Cones can respond to flickering stimuli up to about 7070 Hz. Above this frequency, the light appears as a constant brightness.

Phototransduction Cascade

  1. Photoisomerization: A photon converts 11-cis-retinal to all-trans-retinal.
  2. Opsin Activation: All-trans-retinal activates opsin, a G protein-coupled receptor-like protein.
  3. Transducin Activation: Opsin activates transducin (a G protein) by exchanging GDP for GTP.
  4. Phosphodiesterase Activation: Activated transducin activates cyclic GMP phosphodiesterase.
  5. Cyclic GMP Hydrolysis: Phosphodiesterase hydrolyzes cyclic GMP to GMP, reducing its concentration.
  6. Sodium Channel Closure: Decreased cyclic GMP causes sodium channels to close, leading to hyperpolarization.

Termination and Resetting the Response

  1. Opsin Phosphorylation and Arrestin Binding: Rhodopsin kinase phosphorylates opsin, allowing arrestin to bind and stop transducin activation. The duration of opsin activation determines the response magnitude.
  2. Transducin Inactivation: G protein hydrolyzes GTP to GDP, inactivating phosphodiesterase.
  3. Cyclic GMP Regeneration: Guanylate cyclase rebuilds cyclic GMP from GTP (an energy-expensive process).
  4. Channel Reset: Cyclic GMP reopens sodium channels.
  5. Retinal Recycling: All-trans-retinal is converted back to 11-cis-retinal in support cells and transported back to the photoreceptor.

Continuous Activity and Balance

The system is always active, with both phosphodiesterase and guanylate cyclase constantly breaking down and building up cyclic GMP. Light modulates the balance between these activities. Non-specific cation channels also allow calcium influx. Reduced calcium levels activate guanylate cyclase, while increased calcium inhibits it, maintaining balance.

Threshold and Saturation

  • Threshold: Minimum stimulus required for a response (analogous to perceptual thresholds).
  • Saturation: Maximum response level. Cones have a limited dynamic range (e.g., 1010 mV), posing a challenge for encoding a wide range of brightnesses.
  • Just Noticeable Difference (JND): The smallest perceivable difference in brightness.

Adaptation

Cones adjust their sensitivity to ambient light levels, rapidly resetting to their resting membrane potential (−40-40 mV).

  • Dark Adaptation: Reducing illumination leads to less activated opsin, decreased phosphodiesterase activity, transient increase in cyclic GMP, and opening of sodium channels, causing depolarization. Calcium influx is reduced, activating guanylate cyclase.
  • Guanylate Cyclase Activating Protein: Calcium binds to this protein, slowing down guanylate cyclase activity.
  • Recoverin: Calcium binds to recoverin, slowing down rhodopsin kinase and prolonging opsin activation.
  • The combination of these mechanisms restores the resting membrane potential and increases sensitivity to subsequent light.

Rods vs. Cones

  • Dark Adaptation: Initial adaptation is biochemical. Rods take over after about 5-10 minutes as they rebuild their photopigment.
  • Duplicity Theory: People without rods can only adapt to the level achievable by cones.
  • Retinal Source: Rods and cones use different sources of retinal. Cones regenerate pigment faster thanks to Müller cells. Rods can only get new 11-cis-retinal from the retinal pigment epithelium, while cones can use both RPE and Müller cells.
  • Light Capture: Rods have long outer segments for capturing photons, whereas Cones have shorter outer segments, less sensitive. They saturate less easily.
  • Temporal Resolution: Rods have prolonged responses, limiting them to about 2020 Hz flicker detection, while cones can reach 7070 Hz due to faster response times.
  • Adaptation Efficiency: Rods show less biochemical adaption and saturate, cones adapt efficiently to varying illumination light levels.

Mechanoreceptors: Auditory Hair Cells

Outer hair cells in the cochlea are mechanoreceptors.

  • Membrane potential: −40-40 to −60-60 mV.
  • Neurotransmitter: Glutamate.
  • Transduction: Mechanically gated by stereocilia on the cell's upper surface.

Stereocilia Movement

Tilting the stereocilia bundle towards the tallest stereocilia depolarizes the cell, while tilting it in the opposite direction hyperpolarizes it. Sound waves cause the membranes of the inner ear to oscillate, which in turn causes the stereocilia to oscillate. For low-frequency sounds, the membrane potential follows the sound wave. However, at higher frequencies, hair cells don't manage to hyperpolarize. Frequencies can reach up to 900900 Hz.

  • Strands of glycoprotein connect the tip of a shorter stereocilium to the side of a taller one.
  • Tilting the bundle stretches or slackens the tip links, mechanically gating ion channels.
  • Damage to tip links (experimentally or genetically) results in deafness.

Calcium Influx

  • Tilting the stereocilia towards the tallest row causes calcium influx at the tips of the shorter stereocilia.
  • Mechanically gated channels are non-specific cation channels, allowing calcium and other ions to enter.

Cochlear Fluid and Ion Concentrations

  • Endolymph: The fluid in the cochlear duct is high in potassium and low in sodium.
  • Perilymph: The extracellular fluid elsewhere in the body is high in sodium and low in potassium.
  • Stria Vascularis: Maintains the unique ionic composition of the endolymph.
  • Resting cell polarity of cells of high concentration of potassium within the cells. High levels of sodium on the outside.

Electrical Gradient

  • A +8080 mV potential difference exists between the endolymph and the surrounding extracellular fluid, creating an electrical gradient.
  • Potassium ions are driven into the hair cells by this electrical gradient, causing depolarization.
  • Depolarization is caused by the entry of potassium rather than sodium.

Metabolic Efficiency

  • Voltage-gated potassium channels open to release excess positive charge (potassium) into the perilymph.
  • Metabolic activity is outsourced to the stria vascularis.
  • The cell does not expend energy during depolarization and repolarization.

Hair Cell Response and Adaptation

  • Threshold: Approximately 5050 dB; responses increase with loudness.
  • Saturation: Hair cells saturate at high sound levels.

Adaptation Mechanisms

  • Slow Adaptation: Myosin molecules adjust tension in tip links, altering sensitivity. Tip links can be made tauter or slacker. The tauter it is, the more sensitive it'll be to a tug.
  • Calcium-Mediated Adaptation: Calcium entry interferes with channel opening, reducing response to loud sounds.
  • Damage: Loud noise can damage these structures, causing ringing in the ears (tinnitus).
  • Tinnitus: Leakage from damaged membranes from the loud sounds.