Exam Prep: Channels, Action Potentials, and Vision

Exam Logistics and Advice

• The exam is scheduled for Wednesday.

• A review session will be held immediately after class in the Physics Building.

• Practice questions for bonus points are due by the start of the exam.

• Any academic misconduct will result in a failing grade for the course.

• No questions will be answered during the exam itself.

• Reasons to raise your hand during the exam are limited to: requesting a bathroom break or reporting a missing page in your exam.

• Key Reminder for Taking the Exam:

  • Be on time and sit in your assigned seat.

  • Read all questions very carefully. Exam questions may intentionally alter common phrases (e.g., changing "increase" to "decrease" by a single word) to test careful reading. Students often misread words, substituting what they expect to see, leading to incorrect answers.

  • "None of the above" and "all of the above" are legitimate answer choices in this class, though they are not always the correct answers.

Review of Channels and Action Potentials

• Ion Channels:

  • When an ion enters a channel, it loses its surrounding water shell. The bonds with this water shell must be replaced by interactions within the channel's selectivity filter.

• Nernst Equation:

  • Used to determine the potential of an individual ion.

  • The Nernst potential of an ion is dependent on its charge and the concentration gradient (outside vs. inside the cell).

  • The relationship between the Nernst potential and the membrane potential dictates the direction of ion flow when a channel is open:

    • If the Nernst potential $\approx$ membrane potential, there will be no net ion flow.

    • If the membrane potential $<$ Nernst potential, the ion will flow into the cell.

    • If the membrane potential $>$ Nernst potential, the ion will flow out of the cell.

  • This flow is based on ions moving down their electrochemical gradient.

• Action Potentials (APs):

  • APs are slower processes that involve voltage-gated sodium ($\text{Na}^{+}$) and potassium ($\text{K}^{+}$) channels.

  • Characteristics of APs: They are regenerative, transient, an "all or nothing" response, and include a signal boost process.

  • Initiation Phase: A signal leads to an initial depolarization of the membrane through electrotonic conduction.

  • This initial depolarization must reach a nearby voltage-gated $\text{Na}^{+}$ channel.

  • If the depolarization is above the threshold for that channel to open, the $\text{Na}^{+}$ channel will open.

  • At some point, the voltage-gated $\text{Na}^{+}$ channel will inactivate (not close) and enter a refractory period.

  • Around this membrane potential, voltage-gated $\text{K}^{+}$ channels are triggered to open.

• Summation of Stimuli: Cells can integrate multiple stimuli.

  • Spatial Summation: Multiple cells signal concurrently to one postsynaptic cell.

  • Temporal Summation: A single neuron signals many times in rapid succession to one postsynaptic cell.

  • The core idea is that multiple stimuli occurring around the same time are required to reach a threshold.

• Unidirectional Signal Flow:

  • The unidirectional propagation of APs is achieved through the inactivation of channels.

  • In the inactivated state, the channel prevents ion flow, even if the membrane potential would otherwise allow it to open.

  • For an inactivated channel to return to an open state, it typically must go through a repolarized state.

  • Refractory Period: The time it takes for a channel to transition from an inactivated state back to a state capable of opening.

    • Absolute Refractory Period: During this period, no amount of signal can cause the channel to re-open; it is completely inactivated.

    • Relative Refractory Period: After some time, under certain conditions, a much larger signal than the initial stimulus might be able to re-open the channel.

  • Inactivation creates a "buffer region" behind the propagating signal, preventing it from moving backward.

• Re-establishing Ion Gradients: The question of how cells re-establish ion gradients after depolarization was posed, but the full explanation was not provided in this segment of the transcript, although it implies the action of ion pumps from previous lecture material.

Introduction to Vision: The Eye

• Application: The principles of membrane transport and potentials are applied to understand the function of the eye.

• Visual Perception: Our eyes are not inherently perfect at seeing; the brain plays a significant role in interpreting visual information.

• Electromagnetic Spectrum: The human retina is only sensitive to a very small portion of the entire electromagnetic spectrum.

• Retina Function: The various components of the eye (e.g., lens, cornea) focus light onto the retina.

  • Damage to any part of the light-focusing pathway affects vision.

  • Glaucoma: High pressure of the aqueous humor can distort the light-focusing mechanism, leading to vision impairment.

• Sensitivity vs. Resolution:

  • Periphery of the Retina: Characterized by high sensitivity and lower resolution.

  • Fovea: Characterized by high resolution and lower sensitivity, as light is precisely focused here.

• Rods vs. Cones:

  • Rods: Highly sensitive photoreceptors. They can respond to a single photon, and only $5$ to $7$ photons are needed to sense light.

    • Used for scotopic (dark) vision.

    • Provide black and white vision; colors appear less bright in low light.

  • Cones: Less sensitive than rods, but responsible for photopic (color) vision.

    • Different types of cones absorb different wavelengths of light, allowing for color perception.

Photoreceptors and Photopigments

• Photoreceptor Pigments: Each photoreceptor contains pigments that absorb specific wavelengths of light.

• Rhodopsin (Rod Opsin):

  • Found in rods.

  • Possesses a peak light absorption at approximately $500$ nanometers (nm).

• Cone Opsins:

  • Found in cones.

  • There are three types of cone opsins (for short, medium, and long wavelengths).

  • Short-wavelength cone opsin (responsible for blue light perception) has a peak absorption around $420$ nm.

• Nomenclature Clarification: Although the terms can be confusing, "rhodopsin" often specifically refers to rod opsin. Cones contain "cone opsins." Both are similar gene homo-proteins and function in similar ways.

Signal Transduction in the Retina: Dark Current and Phototransduction

• Neurotransmitter Release: At the other end of the photoreceptor cell, neurotransmitters are released into the synaptic region, signaling to bipolar and horizontal cells.

• Bipolar and Horizontal Cells: These cells receive and process the neurotransmitter signals.

• Potassium Leak Channels: In this intersection, potassium leak channels contribute to hyperpolarization, which reduces the overall neurotransmitter firing rate.

• Light's Effect on Signaling:

  • Under light conditions, less signal is sent from photoreceptors.

  • This reduced signal is then passed to horizontal and bipolar cells.

  • Further reduced signal is sent from bipolar cells to amacrine and ganglion cells.

  • Finally, ganglion cells send less signal to the brain, which is interpreted as "light."

• Advantages of "Inverse" Signaling (Light $\implies$ Less Signal):

  1. Less Noisy: Operating from a depolarized state in the dark and reducing signaling upon light detection is less susceptible to noise.

  2. Increased Dynamic Range: This mechanism dramatically increases the range of light intensities that the eye can perceive.

• Cone Refractory Period and Intensity:

  • The refractory period of cones is longer for brighter flashes of light compared to less bright light.

  • The brain can interpret longer neuronal refractory periods as a more intense light stimulus, helping to distinguish between different levels of brightness.

• The Dark Current:

  • In the absence of light (in the dark), there are high levels of cyclic guanosine monophosphate (cGMP) in photoreceptor cells.

  • These high cGMP levels keep cation channels open.

  • This leads to an influx of sodium ($\text{Na}^{+}$) and some calcium ($\text{Ca}^{2+}$) ions.

  • This ion influx causes the depolarization of the photoreceptor membrane.

  • This depolarization results in continuous neurotransmitter release.

  • This sustained flow of ions in the dark is referred to as the dark current.

• Retinal as a Cofactor:

  • Retinal is a small, non-protein molecule that acts as a cofactor (it is neither an enzyme nor a coenzyme) within the rhodopsin protein.

  • Rod cells contain numerous rhodopsin molecules.

  • Light travels through various cell layers of the retina to reach the very outer segment of the photoreceptor.

  • At the outer segment, within stacked discs of the rod, light is absorbed by a rhodopsin molecule.

  • The absorption of light by retinal causes a conformational change in the retinal molecule (from cis to trans isomer).

  • This change in conformation is the initial event in visual phototransduction --- the process by which photons of light are converted into electrical signals that the brain interprets as vision.

Light Adaptation

• Adaptation Process: Refers to how our eyes adjust to changes in light intensity (e.g., moving from a very bright environment to a dark one).

• Rods' Role in Adaptation: Rods are instrumental in dark adaptation, but they adapt much slower than cones.

  • Full dark adaptation for rods can take around $30$ minutes.

• Mechanism of Adaptation: Adaptation involves adjusting the levels of cGMP within photoreceptor cells.

• Purpose of Adaptation: This process allows the cells to become more sensitive, requiring fewer photons of light to elicit a response, essentially enabling vision in very low light conditions.

• Review of Phototransduction (in the Dark):

  • In the dark, photoreceptors exhibit a high rate of neurotransmitter release.

  • This is due to the depolarization of the membrane, known as the dark current.

  • The dark current is created by the sustained opening of cGMP-gated cation channels.