Physiology of the Heart

Heart Function and Muscle Types

• Smooth muscle relaxation involves various functions including heart rate regulation (chronotropic), impulse conduction (dromotropic), and contraction (inotropic).
• Ejection fraction is a critical measure reflecting the efficiency of the heart's pumping action.

Renin Release

• Juxtaglomerular cells are responsible for the release of renin, which is important for blood pressure regulation.

Hunger and Metabolism

• Ghrelin is released by the stomach and is a key hormone that stimulates hunger.
• Glucose metabolism is influenced by inhibiting insulin release and stimulating gluconeogenesis and glycolysis, indicating a complex regulatory mechanism.

Lipolysis and Salivary Secretion

• Lipolysis refers to the breakdown of fats, playing a role in energy metabolism.
• Salivary secretion can thicken under certain physiological states, affecting digestion.

Neurotransmitters and Mood Disorders

• Serotonin, norepinephrine, and dopamine are neurotransmitters implicated in depression, a leading mood disorder.
• NMDA and AMPA receptors, types of glutamate receptors, are involved in neuronal excitability and synaptic plasticity.

NMDA Receptors and Neurotoxicity

• NMDA receptor activation leads to significant physiological responses, including sodium channel modulation.
• Amantadine is used to block NMDA receptors, particularly in conditions like Parkinson's disease, although side effects may include hallucinations and ankle edema.

ACh and Synaptic Function

• Acetylcholine (ACh) can have varied effects on target cells, including excitation, inhibition, or both, based on receptor type.
• The action of ACh is primarily determined by the specific receptor it binds to, affecting statics during synaptic transmission.

Receptor Types and Mechanisms

• Muscarinic receptors are G protein-coupled receptors that lead to intracellular signal transduction, activating phospholipase C and potassium channels while inhibiting adenylate cyclase.
• Nicotinic receptors are ionotropic receptors operating via ligand-gated ion channels, enabling rapid synaptic transmission at neuromuscular junctions.

Distinction of Nicotinic Receptors

• Two main types of nicotinic receptors exist: Nm (neuromuscular junction) and Nn (postganglionic cell body), each with specific blockers like d-Tubocurarine and hexamethonium respectively.

Chemical Synapses

• Ionotropic Receptors

  • Produce fast synaptic actions lasting milliseconds.
  • Commonly involved in rapid behaviors, such as reflex actions.
  • Example: Nicotinic acetylcholine receptors (AchR) at neuromuscular junctions activate ion channels, causing depolarization and muscle fiber activation.

• Metabotropic Receptors

  • Generate slower synaptic actions lasting seconds to minutes.
  • Function as reinforcing pathways in learning processes.
  • Example: Muscarinic acetylcholine receptors linked to G proteins at cardiac synapses cause hyperpolarization and inhibit cardiac excitation.

Neurotransmitter Requirements

• Must be synthesized in the presynaptic neuron.
• Should be present in sufficient quantities at the presynaptic terminal to affect postsynaptic neurons.
• Must mimic endogenous transmitter actions when administered externally.
• Requires a mechanism for removal from the synaptic cleft.

Catecholamine Transmitters

• Key catecholamines:

  • Dopamine
  • Norepinephrine
  • Epinephrine (adrenaline)

• Norepinephrine in the CNS originates from the locus ceruleus, affecting many brain regions.

• In the PNS, it serves as a neurotransmitter for postganglionic sympathetic neurons.

Biosynthesis of Catecholamines

• Tyrosine Hydroxylase: Converts tyrosine to L-DOPA; rate-limiting step for dopamine and norepinephrine synthesis.
• Dopamine Hydroxylase: Converts dopamine to norepinephrine; tightly associated with aminergic vesicles.
• Phenylethanolamine-N-methyltransferase: Converts norepinephrine to epinephrine in the adrenal medulla.
• Different neurons express different biosynthetic enzymes, influencing catecholamine type produced.

Dopamine Receptors

• Five receptor subtypes: D1 to D5.
• D1 and D5 increase cAMP levels; D2, D3, and D4 decrease cAMP levels.
• Actions of dopamine on neurons depend on the receptor type present.

Synaptic Transmission

• Action potentials trigger voltage-sensitive calcium channels, increasing intracellular calcium levels.
• Elevated calcium promotes synaptic vesicle fusion and neurotransmitter release into the synaptic cleft.
• Release of neurotransmitters can be blocked by botulinum toxin.

Acetylcholine Degradation

• Acetylcholine is degraded by acetylcholinesterase in the synaptic cleft into choline and acetate.
• True choline esterase is specific to acetylcholine and is vital for life, while pseudocholine esterase is nonspecific and found in various tissues.

Types of Receptors

• Nicotinic Receptors:

  • Ligand-gated ion channels that cause depolarization.
  • Two main types: Nm (neuromuscular junction) and Nn (neuronal).
  • Nm receptors can be blocked by d-tubocurarine.

• Muscarinic Receptors:

  • G protein-coupled receptors that activate phospholipase C, inhibit adenylate cyclase, and modulate potassium and calcium channels.

Electrotonic Transmission

• Electrical synapses transmit both depolarizing and hyperpolarizing currents.
• Signal transmission resembles passive propagation of subthreshold electrical signals along axons.

Rectifying Synapses

• Voltage-dependent gates in some gap junctions allow conduction of depolarizing current only in one direction.

Electrical Synapses

• Electrical synapses consist of gap-junction channels formed by connexons (hemichannels) in both presynaptic and postsynaptic neurons.
• Each connexon is made up of six connexin subunits, facilitating direct communication between cells.
• Modulation of gap junctions is influenced by cytoplasmic pH, calcium levels, and released neurotransmitters.

Role of Gap Junctions in Glial Function

• Astrocytes in the brain utilize gap junctions to establish a glial network.
• Gap junctions enhance communication in Schwann cells and aid in maintaining myelin and small molecule transport.
• Genetic diseases such as Charcot-Marie-Tooth syndrome and congenital deafness arise from mutations in connexin genes affecting gap-junction function.

Chemical Synapse Process

• Neurotransmitter molecules are packaged into synaptic vesicles for signaling.
• Chemical substances fall into two main categories: small-molecule transmitters and neuroactive peptides.

Neurotransmitter Categories

• Small-molecule transmitters are stored in small vesicles (40 nm) and released at active zones; examples include acetylcholine, GABA, and glycine.
• Neuroactive peptides are stored in large dense-core vesicles (70–250 nm) and are released similarly to secretory glands.

Acetylcholine (ACh)

• ACh is synthesized from choline and is released at neuromuscular junctions and autonomic nervous system synapses.
• Synthesis involves a rate-limiting step where choline is taken up and acetylated by choline acetyltransferase.

Acetylcholine Transmission Mechanism

• ACh is stored in vesicles; upon action potential, calcium influx prompts vesicle fusion and release of ACh.
• Degradation occurs through acetylcholinesterase, resulting in choline and acetate.

Acetylcholinesterase Types

• Two types: True choline esterase (specific to ACh) and pseudo choline esterase (non-specific, present in plasma and synthesized in the liver).

Receptor Types

• Nicotinic receptors: ligand-gated ion channels that mediate fast responses at the neuromuscular junction.
• Muscarinic receptors: G protein-coupled receptors that mediate slow, biochemical responses; divided into two types (Nm for neuromuscular junction, Nn for postganglionic neurons).

Ionotropic vs. Metabotropic Receptors

• Ionotropic receptors mediate rapid synaptic responses through direct ion channel activation.
• Metabotropic receptors produce slower responses through G protein activation and downstream signaling.

Catecholamine Transmitters

• Include dopamine, norepinephrine, and epinephrine; critical for various CNS functions.
• Norepinephrine originates from neurons in the locus ceruleus and is vital in the sympathetic nervous system.

Catecholamine Synthesis

• Tyrosine hydroxylase converts tyrosine to l-DOPA; this is the rate-limiting step for dopamine and norepinephrine synthesis.
• Norepinephrine is synthesized in neurons and may be methylated in the adrenal medulla to form epinephrine.

Dopamine Receptors

• Five subtypes (D1-D5) with different effects on cAMP levels.
• Receptor subtype determines the functional impact of dopamine on target neurons.

Glutamate

• Major excitatory neurotransmitter in the CNS, produced from α-ketoglutarate.
• Acts through specific transporters for reuptake, converting back to glutamine in glial cells for recycling.

Glycine Transmission

• Key inhibitory neurotransmitter for spinal cord interneurons, synthesized from serine.
• Degradation occurs via a glycine cleavage system involving multiple proteins.

GABA

• Major inhibitory neurotransmitter in the CNS, found in high concentrations.
• Serves crucial roles in various neuronal circuits and is the primary inhibitory neurotransmitter for spinal cord interneurons and multiple brain regions.

What is Consciousness?

• Defined as emerging from brain systems that both create content and regulate consciousness levels.
• Content of consciousness encompasses processed information through sensory, motor, emotional, and memory systems.
• Level of consciousness impacts cognitive functions and is controlled by specialized cortical and subcortical systems.
• Key mnemonic for consciousness: AAA - Alertness, Attention, Awareness.
• Alertness is necessary for meaningful responses; attention facilitates selective information processing; awareness allows for experiences to be reportable later.

The Consciousness System

• Specialized brain networks critically control levels of consciousness.
• Dependent on both cortical and subcortical structures.

Cortical Components

• Higher-order heteromodal association cortex includes:
  • Medial regions: medial frontal, anterior cingulate, posterior cingulate, medial parietal (precuneus, retrosplenial).
  • Lateral regions: lateral frontal, anterior insula, orbital frontal, lateral temporal-parietal association cortex.
• Individual components of higher-order cortex play vital roles in specific cognitive functions across hemispheres.
• Involvement in task-positive networks (externally oriented attention) and task-negative networks (default mode at rest).

Subcortical Components

• Includes upper brainstem activating systems, thalamus, hypothalamus, and basal forebrain.
• Additional structures: portions of basal ganglia, cerebellum, amygdala, claustrum.
• Multiple neurotransmitter systems involved: acetylcholine, glutamate, GABA, norepinephrine, serotonin, dopamine, histamine, and orexin.

Mechanisms of Consciousness

• Proposed mechanisms include synchronized oscillations, slow cortical potentials, connectivity, information integration, and recurrent/global neuronal processes.
• Further research is needed for clarity on physiological mechanisms.

The Cortex and Arousal

• Cerebral cortex is the primary input for subcortical arousal systems.
• Stimulation of higher-order heteromodal frontoparietal association cortex elevates arousal.
• Unilateral cortical lesions have minimal effects on consciousness; bilateral lesions can lead to coma.

Attention and Consciousness

• Attention and consciousness exhibit both similarities and differences.
• Attention is necessary for consciousness but not identical to it.

Hemispheric Dominance of Attention

• Right hemisphere is dominant for spatial attention in most individuals.
• Right-sided lesions may lead to hemineglect affecting the left side of the body.
• Left hemisphere (Broca’s Area) is more language-oriented, positioning language as a content component, not a regulator.

Affect, Motivation, and Attention

• Emotional motivation significantly influences attention task performance.
• Orbital frontal cortex and limbic circuits are crucial in driving motivational aspects of attention.

The Binding Problem

• Addresses how diverse aspects of perception unify into a single conscious experience.

This quiz covers key concepts related to the physiology of the heart, including smooth muscle relaxation and the effects of heart rate and impulse conduction. It touches on various muscular and nervous system components involved in regulating cardiac functions and attention. Test your understanding of these crucial physiological mechanisms!