Human Physiology: Cellular Mechanisms

Every organ system, from the cardiovascular system to the brain, depends on events that happen at the level of individual cells. Cells maintain internal stability, communicate with neighbors, convert signals into action, and generate electrical activity that coordinates tissue function. These foundational cellular mechanisms are not abstract concepts. They explain how the kidney concentrates urine, how skeletal muscle contracts, how hormones direct metabolism, and why disruptions can lead to disease.

This article focuses on four core pillars of cellular physiology: membrane transport, action potentials, cell signaling, and second messengers.

Membrane transport: controlling what enters and leaves the cell

The cell membrane is a selectively permeable barrier. It separates intracellular fluid from extracellular fluid, allowing cells to regulate ion concentrations, nutrient uptake, and waste removal. Because the membrane’s lipid bilayer is hydrophobic, most charged or polar molecules require specialized transport processes.

Passive transport: moving down gradients

Passive transport does not require direct cellular energy input. It relies on gradients, which represent stored potential energy.

Simple diffusion allows small nonpolar molecules, such as oxygen and carbon dioxide, to cross the membrane directly. Rate depends on the concentration gradient and membrane permeability.

Facilitated diffusion uses membrane proteins to move substances down their electrochemical gradients. This is critical for polar molecules like glucose and for ions. A classic example is glucose entry into many cells through specific carrier proteins, which increases transport speed and selectivity compared with diffusion through the lipid bilayer.

Osmosis is the net movement of water across a semipermeable membrane. Water shifts toward the side with higher effective solute concentration, shaping cell volume. In physiology, osmosis underlies fluid movement across capillary walls and the handling of water in renal tubules.

Active transport: moving against gradients

Active transport moves substances against their electrochemical gradients, requiring energy. This is essential for maintaining the unequal ion distributions that make electrical signaling possible.

Primary active transport uses ATP directly. The best-known example is the sodium-potassium pump, which maintains high intracellular potassium and low intracellular sodium. That distribution supports resting membrane potential and provides the driving force for many secondary transport processes.

Secondary active transport uses the energy stored in one gradient to move another substance uphill. For instance, sodium moving down its gradient can power the uphill movement of glucose in certain epithelial tissues. This type of coupling is central to absorption in the intestine and reabsorption in the kidney.

Channels, carriers, and gating

Transport proteins fall broadly into channels and carriers:

• Ion channels form pores that allow rapid, selective ion movement. Many are gated, meaning they open or close in response to voltage, ligands, or mechanical forces.
• Carriers (transporters) bind their cargo and undergo conformational changes to move it across. They tend to be slower than channels but highly specific.

These differences matter in real tissues. Rapid signaling in neurons depends on ion channels, while regulated nutrient transport often relies on carriers.

Membrane potentials and action potentials: the language of excitable cells

Many cells are electrically excitable, particularly neurons, skeletal muscle, cardiac muscle, and some endocrine cells. Their membranes maintain a voltage difference across the lipid bilayer called the membrane potential.

Resting membrane potential: gradients and permeability

Resting membrane potential arises from two main factors:

1. Ion gradients across the membrane, maintained largely by active transport.
2. Selective permeability, especially high resting permeability to potassium in many cells.

At rest, potassium tends to diffuse out of the cell through leak channels, leaving behind negative charge and making the inside relatively negative. The balance between chemical drive and electrical pull sets the resting potential.

Although multiple ions contribute, the key idea is that the resting membrane potential reflects which ions the membrane is most permeable to at baseline.

Action potentials: rapid, regenerative electrical events

An action potential is a brief, all-or-none change in membrane potential that propagates along excitable membranes. It allows fast communication over distance without signal decay.

Action potentials generally follow these phases:

• Depolarization: voltage-gated sodium channels open, sodium enters, and the membrane potential becomes less negative.
• Repolarization: sodium channels inactivate and voltage-gated potassium channels open, allowing potassium to exit and restoring negativity.
• After-hyperpolarization (often): potassium conductance remains elevated briefly, pushing the membrane potential below its resting level.

Two important physiological principles stem from channel behavior:

• Threshold: a critical depolarization is needed to open enough sodium channels to trigger a regenerative spike.
• Refractory periods: sodium channel inactivation limits how quickly another action potential can occur, shaping firing frequency and direction of propagation.

Conduction and speed

Action potentials move because depolarization in one region influences adjacent membrane regions. Conduction speed depends on properties such as axon diameter and electrical insulation. In many vertebrate neurons, insulating myelin increases conduction efficiency by restricting ion exchange to discrete nodes, enabling rapid saltatory propagation.

Cell signaling: how cells detect information and respond

Cells constantly receive signals from their environment, including neurotransmitters, hormones, growth factors, and local mediators. Cell signaling links an external message to an internal response, such as secretion, contraction, gene expression, or metabolic change.

Receptors: translating outside signals into cellular actions

Major receptor categories include:

• Ligand-gated ion channels: binding of a signaling molecule directly opens an ion channel, producing fast responses. This is common in synaptic transmission.
• G protein-coupled receptors (GPCRs): binding activates intracellular G proteins, which then modulate enzymes or channels. GPCR signaling is versatile and common in physiology.
• Enzyme-linked receptors: binding activates intrinsic enzymatic activity or associated enzymes, often leading to phosphorylation cascades important in growth and metabolism.
• Intracellular receptors: lipid-soluble signals can cross the membrane and bind receptors inside the cell, frequently altering gene transcription. These pathways tend to act more slowly but have lasting effects.

Specificity, amplification, and termination

Effective signaling requires more than message delivery:

• Specificity depends on receptor expression. The same hormone can produce different outcomes in different tissues because receptor types and downstream proteins differ.
• Amplification allows a small signal to produce a large response. A single activated receptor can lead to many activated intracellular molecules.
• Termination prevents continuous activation. Cells remove ligands, deactivate signaling proteins, break down second messengers, and reset ion channel states.

These principles explain why some drugs act quickly but briefly, while others have slower, sustained effects.

Second messengers: building intracellular responses

Many receptors do not directly cause the final cellular effect. Instead, they trigger the production or release of second messengers, small intracellular molecules that distribute and amplify the signal.

Common second messenger systems

Several second messenger pathways are central in human physiology:

• Cyclic AMP (cAMP): commonly produced after GPCR activation. It activates protein kinases that phosphorylate target proteins, altering enzyme activity, ion channel behavior, and gene regulation.
• Inositol trisphosphate (IP3) and diacylglycerol (DAG): generated from membrane phospholipids. IP3 often promotes calcium release from intracellular stores, while DAG activates protein kinases at the membrane.
• Calcium (Ca²⁺): acts as both an ion and a second messenger. Cells tightly regulate cytosolic calcium because it influences contraction, secretion, metabolism, and transcription. Calcium signals are often shaped as brief spikes or waves, not just sustained elevations.
• Nitric oxide (NO): a diffusible messenger that can move between cells and influence smooth muscle tone and local blood flow by activating intracellular signaling pathways.

Why second messengers matter physiologically

Second messenger systems provide flexibility:

• They convert a single receptor event into multiple downstream effects.
• They allow integration of signals, so a cell can respond differently depending on context.
• They enable fine control through feedback, including positive feedback that sharpens responses and negative feedback that stabilizes systems.

A practical example is how a cell can shift from a rapid response, such as changing ion channel opening, to a longer-term adjustment, such as altering gene expression, using the same initial signaling pathway but different downstream branches.

How these mechanisms integrate across organ systems

Membrane transport establishes gradients and homeostasis. Action potentials use those gradients to convey fast information. Cell signaling tells cells when to change behavior. Second messengers translate receptor activation into coordinated intracellular actions.

In the nervous system, ion channels and action potentials drive communication, while second messengers tune synaptic strength and cellular responsiveness. In muscle, electrical activity couples to calcium signaling to produce contraction. In endocrine physiology, hormone binding triggers second messenger cascades that reshape metabolism and gene expression. In epithelial tissues like kidney and intestine, transporters use gradients to move solutes and water, directly determining fluid balance.

Understanding these cellular mechanisms is not optional background. It is the framework that makes organ-level physiology coherent and clinically meaningful.