Ion Channels in Vertebrates

Ion Channels

• Ion channels are proteins in cell membranes that allow passage of ions.
• They are crucial for nerve impulses and other cellular functions.
• Various types exist, including leak channels, ligand-gated, mechanically gated, and voltage-gated channels.

Aims and Objectives

• The aim is to define types of ion channels in vertebrates.
• To comprehend the molecular structure and function of vertebrate voltage-gated Na+ and Ca2+ channels.
• To define key Ca2+ channel types and their locations.

Why Do Ion Channels Exist?

• A buildup of negative ions inside the cell membrane and an equal positive buildup outside creates a resting membrane potential.
• This potential difference (measured in mV) is crucial for cell function, serving as potential energy.
• The difference in charge across the membrane directly relates to the potential energy level.

Evidence for Membrane Potential

• Hodgkin and Huxley (1952) used microelectrodes to measure this resting membrane potential.
• A recording microelectrode is inserted inside the cell, a reference electrode is placed outside in the extracellular fluid, and connected to a voltmeter for accurate readings of the voltage difference across the membrane.

Unequal Ion Distribution

• The extracellular fluid (ECF) is rich in sodium (Na+) and chloride (Cl−) ions.
• The cytosol is rich in potassium (K+) and negatively charged molecules (phosphate and proteins) that cannot readily leave the cell.
• K+ leakage channels enable more K+ ions to diffuse out of the cell compared to Na+ ions entering.
• Na+/K+ ATPase pumps maintain this unequal distribution by actively pumping Na+ out of the cell and K+ into the cell.

Types of Ion Channels

• Leak channels: Randomly open and close; more numerous in neurons.
• Ligand-gated channels: Open when a signaling molecule (ligand) binds. Found on dendrites and cell bodies.
• Mechanically gated channels: Open in response to physical stimuli (e.g., touch, vibration). Found in sensory receptors.
• Voltage-gated channels: Open in response to changes in membrane potential. Crucial for propagating nerve impulses.

Neuronal Ion Channels

• The plasma membrane of neurons contains various types of ion channels (chemically gated, voltage gated Na+, and voltage gated Ca2+).
• These ion channels are strategically located along the neuron to facilitate signaling.

Voltage-gated Sodium Channels

• They are crucial for nerve impulse generation.
• Composed of three subunits, with one α subunit forming the pore.
• The α subunit also has activation and inactivation gates.
• The β subunit has a smaller size (~30 kDa).

Sodium Channel Domains and Functions

• The channel has 24 transmembrane segments organised into 4 domains (S1-S6).
• The domains facilitate voltage sensing and form the pore.
• A 2000- amino acid protein chain forms the channel.

Molecular Mechanism of Fast Inactivation

• Inactivation gates close the channel after opening rapidly.
• Amino acid residues in the inactivation gate form a latch that keeps the channel closed.

Calcium Channels

• The α1 subunit forms the pore; α2, β, γ, and δ subunits are auxiliary subunits.
• These subunits are not directly involved in voltage-gating or Ca2+ conduction but regulate the channels.
• Various types of Ca2+ channels exist (L, N, P, Q, R, T).

Ca2+ Signals Initiate Physiological Processes

• Ca2+ channel activation by electrical signals initiates cellular events, including synaptic transmission and muscular contraction.
• Ca2+ channels regulate numerous cellular processes.

Structure of Calcium Channels

• Calcium channels consist of a large protein with four repeated domains.
• Each domain contains six transmembrane segments and intracellular loops—crucial for signaling and protein binding.

Example - Calmodulin

• Calmodulin is a protein that binds to Ca2+ and regulates various cellular processes.
• Calmodulin binds Ca2+ in response to increased levels, which initiates changes in cellular activity.

Types of Calcium Channels

• L-type: Long lasting, slow inactivation, high activation threshold. In cardiac muscle.
• T-type: Transient, fast inactivation, low activation threshold. In SA node, endocrine cells, etc.