Human Anatomy & Physiology I(8)
Cellular Biology
Chapter Three Overview
Membrane Potential
Resting Membrane Potential (RMP):
Defined as the electrical potential energy produced by the separation of oppositely charged particles across the plasma membrane in all cells.
The difference in electrical charge between two points is referred to as voltage.
Cells that have a charge are described as being polarized.
Voltage is present only at the membrane surface; both the cytoplasmic side and extracellular fluid remain neutral.
The membrane voltage typically ranges from -50 to -100 mV in various cell types, indicating that the inside of the cell is more negative relative to the outside.
Key Player in RMP: Potassium (K+)
K+ Diffusion:
K+ ions diffuse out of the cell through K+ leakage channels, moving down their concentration gradient.
Negatively charged proteins (anions) within the cell cannot leave, causing the cytoplasmic side of the cell membrane to become more negatively charged.
As K+ exits, the interior of the cell becomes increasingly negative, which pulls K+ back in due to the electrical gradient.
Equilibrium:
A resting membrane potential (RMP) is established when the outward drift of K+ is balanced by the inward pull of the negative charge, creating an electrochemical gradient that defines the RMP.
Electrochemical Gradient of K+: Sets the RMP primarily due to stronger permeability of the membrane to K+ compared to Na+.
Sodium's Role in RMP
Influence of Na+:
In many cells, Na+ also impacts the RMP due to its attraction to the negativity inside the cell.
Na+ can raise the RMP closer to -70 mV if it enters the cell; however, ion membranes are more permeable to K+, hence K+ has the primary influence on RMP.
Chloride Ion (Cl-) does not have a significant influence on RMP because its concentration and electrical gradients are balanced.
Mechanism of RMP Generation
Role of K+ in RMP
Process Overview:
K+ leaks out of the cell, creating a negative charge on the inside of the plasma membrane.
A dynamic equilibrium is achieved at -90 mV when the outward concentration gradient for K+ exiting the cell is evenly matched by the electrical gradient pulling K+ back in.
Active Transport and Electrochemical Gradients
Na+-K+ Pump Functions:
The RMP is upheld primarily through the Na+-K+ pump which actively transports 3Na+ ions out of the cell and 2K+ ions back in, maintaining a concentration gradient.
The pump establishes a steady state as the active transport rate for Na+ out balances the rate of passive Na+ diffusion in.
Neurons and muscle cells can temporarily disrupt this steady state RMP by activating gated Na+ and K+ channels.
Cell Cycle Overview
Definition and Stages
Cell Cycle:
It is a series of changes a cell undergoes from formation to reproduction.
Two major periods include:
Interphase: where the cell grows and performs routine activities.
Mitotic Phase: where the cell divides into two.
Interphase Description
Role of Interphase:
It spans the period from cell formation to cell division, during which the cell grows and prepares for division.
Nuclear material is found in an uncondensed chromatin state.
Interphase is further divided into three subphases:
G1 (Gap 1): involved with vigorous growth and metabolism.
S (Synthesis): where DNA replication occurs.
G2 (Gap 2): preparation phase for cell division.
DNA Replication Steps
Process of DNA Replication:
Before division, DNA is copied as the double-stranded helix unwinds and unzips. Each original strand serves as a template for a new complementary strand.
RNA lays down a short primer for replication initiation.
As replication progresses, DNA polymerase attaches to the primer and synthesizes new strands simultaneously.
Each resulting double-stranded DNA consists of one old (parent) strand and one newly synthesized strand, a process known as semiconservative replication.
Cell Division (M Phase)
Overview of Mitosis
Definition of Mitosis:
It is defined as the process of nuclear division where duplicated DNA is equally distributed to two daughter cells. Key phases of mitosis include:
Prophase: Chromatin condenses to form visible chromosomes.
Metaphase: Chromosomes align at the cell equator.
Anaphase: Centromeres split, and sister chromatids are pulled apart to opposite poles.
Telophase: Chromatids at pole locations begin to uncoil back into chromatin.
Telophase and Cytokinesis
Telophase Description:
Begins once chromosomal movement ceases; each set of chromosomes uncoils and new nuclear envelopes form around each.
Nucleoli reappear, and the mitotic spindle dissolves.
At this stage, the cell is temporarily binucleate (possessing two nuclei).
Cytokinesis Function:
This is the division of the cytoplasm, beginning during late anaphase and continuing through telophase.
A contractile ring of actin filaments forms the cleavage furrow, leading to two daughter cells splitting apart.
Control of Cell Division
Regulatory Signals:
Cells have “Go” and “Stop” signals that dictate their division status.
Go Signals: incluse critical surface-to-volume ratios, various chemical signals (growth factors and hormones).
Stop Signals: availability of space; normal cells will cease dividing upon contact with neighboring cells, a phenomenon termed contact inhibition.
Cellular Biology
Chapter Three Overview
Membrane Potential
Resting Membrane Potential (RMP):
Defined as the electrical potential difference (voltage) across the plasma membrane, resulting from the separation of oppositely charged ions in all living cells, especially excitable cells like neurons and muscle cells. This separation creates stored potential energy.
The difference in electrical charge between two points is referred to as voltage. For biological membranes, this is typically measured in millivolts (mV).
Cells that exhibit a net charge separation across their membrane are described as being polarized.
The significant voltage difference is localized strictly at the membrane surface (a thin layer), while the bulk of the cytoplasmic side and extracellular fluid remain electrically neutral, containing equal numbers of cations and anions.
The membrane voltage typically ranges from -50 to -100 mV in various cell types, with a common value of -70 mV for many neurons, indicating that the inside of the cell is significantly more negative relative to the outside.
Key Player in RMP: Potassium (K+)
K+ Diffusion:
K+ ions, which are highly concentrated inside the cell, continuously diffuse out of the cell through specialized K+ leakage channels, moving down their steep concentration gradient. The cell membrane is much more permeable to K+ than to other ions at rest.
Large, negatively charged proteins (anions) and other organic phosphates are trapped within the cell and cannot follow K+ when it exits. This differential movement causes the cytoplasmic side of the cell membrane to become progressively more negatively charged as K+ leaves.
As K+ exits, increasing the negativity inside the cell, an electrical gradient is established that pulls K+ back into the cell, opposing its outward chemical gradient.
Equilibrium:
A resting membrane potential (RMP) is established when the outward chemical gradient (concentration gradient) driving K+ out of the cell is precisely balanced by the inward electrical gradient pulling K+ back in. At this point, there is no net movement of K+ across the membrane.
Electrochemical Gradient of K+: This specific balance for K+ at approximately -90 mV primarily sets the RMP for most cells due to the membrane's much stronger permeability to K+ compared to Na+.
Sodium's Role in RMP
Influence of Na+:
While K+ is the primary determinant, Na+ also impacts the RMP, though to a lesser extent, because a small number of Na+ leakage channels are also present in the membrane.
Na+ ions, highly concentrated outside the cell, slowly diffuse into the cell down their electrochemical gradient (attracted by both its concentration gradient and the negativity inside the cell).
This slow influx of Na+ counteracts some of the K+ efflux, making the RMP slightly less negative than the K+ equilibrium potential, typically raising it closer to -70 mV (e.g., from -90mV to -70mV). However, because ion membranes are significantly more permeable to K+ than to Na+ at rest, K+ retains the primary influence on RMP.
Chloride Ion (Cl-) typically does not have a significant influence on RMP because its concentration gradient (higher outside) and electrical gradient (pulled out by negative inside) are usually balanced, leading to little net movement across the membrane in many resting cells.
Mechanism of RMP Generation
Role of K+ in RMP
Process Overview:
The initial and primary step in RMP generation is the leakage of K+ out of the cell through numerous K+ leakage channels. This movement leaves behind large, impermeable anionic proteins inside the cell, thereby creating a negative charge on the inside of the plasma membrane.
A dynamic equilibrium is achieved at approximately -90 mV (the equilibrium potential for K+), where the outward force of the concentration gradient for K+ exiting the cell is precisely and evenly matched by the electrical gradient pulling K+ back in. This establishes the foundational component of the RMP.
Active Transport and Electrochemical Gradients
Na+-K+ Pump Functions:
While leakage channels establish the initial ion gradients and contribute to the RMP, the long-term maintenance of the RMP and the concentration gradients of Na+ and K+ is upheld primarily through the Na+-K+ pump (Na+/K+-ATPase).
This electrogenic pump actively transports 3 Na+ ions out of the cell for every 2 K+ ions it pumps back into the cell, consuming ATP in the process. This differential movement of charge contributes a small but significant direct negative charge to the RMP (about -3 to -5 mV).
The pump establishes a crucial steady state by continuously countering the passive leakage of both Na+ into the cell and K+ out of the cell. The active transport rate for Na+ out balances the rate of passive Na+ diffusion in, and similarly for K+.
Neurons and muscle cells, classified as excitable cells, can temporarily disrupt this steady state RMP by activating specific voltage-gated Na+ and K+ channels, leading to rapid changes in membrane potential (action potentials).
Cell Cycle Overview
Definition and Stages
Cell Cycle:
It is a highly regulated series of events that a cell undergoes from the time it is formed until it reproduces by dividing into two daughter cells. This process ensures accurate DNA replication and segregation.
The two major periods within the cell cycle include:
Interphase: Representing about 90% of the cell's lifespan, this is the period where the cell grows, carries out its normal metabolic functions, prepares for division, and duplicates its DNA.
Mitotic (M) Phase: This shorter period involves the actual division of the nucleus (mitosis) and the cytoplasm (cytokinesis) into two genetically identical daughter cells.
Interphase Description
Role of Interphase:
It spans the period from the end of one cell division to the beginning of the next, during which the cell grows in size, synthesizes proteins, and meticulously prepares for cell division by duplicating its genetic material.
During interphase, the nuclear material, DNA, is found in an uncondensed, diffuse state known as chromatin, making it accessible for transcription and replication.
Interphase is further divided into three main subphases:
G1 (Gap 1): This is a period of vigorous cell growth and metabolism. Cells increase in size, synthesize proteins and organelles. A cell may exit the cell cycle here to enter a quiescent phase known as G0, where it performs its specialized functions without dividing.
S (Synthesis): This crucial phase is where DNA replication occurs. Each chromosome is duplicated, resulting in two identical sister chromatids attached at the centromere. Histones are also synthesized during this phase.
G2 (Gap 2): This is a relatively brief but important preparation phase for cell division. The cell continues to grow, synthesizes enzymes and proteins required for mitosis, and ensures that DNA replication is complete and any errors are repaired. Centrioles also finish duplicating here.
DNA Replication Steps
Process of DNA Replication:
Before a cell can divide, its entire DNA content must be accurately copied to ensure each daughter cell receives a complete set of genetic instructions. This process is known as DNA replication.
The double-stranded helix of DNA unwinds and unzips, much like a zipper, at specific origins of replication, facilitated by the enzyme helicase which breaks the hydrogen bonds between complementary base pairs.
Each original (parent) strand then serves as a precise template for the synthesis of a new complementary strand.
An enzyme called primase lays down a short RNA primer, which provides a starting point (a free 3'-OH group) for DNA polymerase, as DNA polymerase cannot initiate synthesis de novo.
As replication progresses, DNA polymerase attaches to the primer and synthesizes new DNA strands continuously in the 5' to 3' direction along the leading strand and discontinuously in short segments (Okazaki fragments) on the lagging strand.
Each resulting double-stranded DNA molecule consists of one old (parent) strand and one newly synthesized strand, a mechanism termed semiconservative replication. This ensures high fidelity in genetic inheritance.
Cell Division (M Phase)
Overview of Mitosis
Definition of Mitosis:
It is defined as the process of nuclear division in eukaryotic cells, where the duplicated chromosomes are accurately and equally distributed to two new daughter nuclei. This results in two genetically identical somatic cells.
Key phases of mitosis include:
Prophase: The initial and longest phase of mitosis. Chromatin fibers condense and coil tightly to form visible, discrete chromosomes, each consisting of two identical sister chromatids joined at the centromere. The nucleoli disappear, and the mitotic spindle fibers (microtubules) begin to form from the centrosomes, which move apart. The nuclear envelope also begins to break down.
Metaphase: This is the shortest phase. The chromosomes align precisely at the cell's equatorial plane, forming the metaphase plate. Each centromere lies exactly on the plate, and the centrosomes are at opposite poles of the cell, with spindle fibers attached to the kinetochores of each chromatid.
Anaphase: This is the dramatic phase where sister chromatids abruptly separate. The centromeres split simultaneously, and the now individual daughter chromosomes are pulled apart by shortening kinetochore microtubules towards opposite poles of the cell. This movement is powered by motor proteins.
Telophase: This phase begins once chromosomal movement ceases and the identical sets of chromosomes arrive at opposite poles. The chromosomes begin to uncoil and decondense back into diffuse chromatin. New nuclear envelopes form around each set of chromosomes, and nucleoli reappear within the new nuclei.
Telophase and Cytokinesis
Telophase Description:
Begins once chromosomal movement to the poles ceases. The separated chromosomes at each pole begin to uncoil and decondense, reverting to their diffuse chromatin state. New nuclear envelopes form from fragments of the parent nuclear envelope and the endomembrane system around each set of chromosomes.
Nucleoli reappear within the newly forming nuclei, and the mitotic spindle fibers completely dissolve. At this stage, the cell is temporarily binucleate, possessing two full nuclei within a single cytoplasm before cytoplasmic division.
Cytokinesis Function:
This is the final stage of cell division, representing the division of the cytoplasm. It typically begins during late anaphase and continues through telophase, overlapping with the nuclear division process.
A contractile ring of actin microfilaments and myosin proteins forms just beneath the plasma membrane in the middle of the cell. This ring constricts, forming a visible indentation called the cleavage furrow.
The cleavage furrow deepens progressively, pinching the cell into two separate, genetically identical daughter cells, each with its own nucleus and complete set of organelles.
Control of Cell Division
Regulatory Signals:
Cell division is tightly regulated by internal and external