Readers will understand and retain:
How the heart functions at the ionic-molecular level

• The teleology of the ion-kinetic mechanisms of the ionic-molecular microcosm
• How three little ions produce conduction through, and contraction of, the heart
• The simple ionic mechanism of cell-to-cell myocardial conduction
• How ion movement translates into vectors
• The movement of ions that produces EKG recordings
• How the atria contract without backflow into the great veins and pulmonary veins
• Why there are automaticity foci in the large vein ostia of the atria
• The homeostatic necessity of automaticity foci in emergency situations
• A simplified methodology for understanding autonomic function
• How troponin components participate in myocyte contraction and relaxation
• TnC, TnI, and TnT function
• Size of ions matters
• Why ion-kinetic (ion-moving) structures like ion channels are essential to cell function
• How the ion pumps produce the gradients that drive ions through ion channels and ion exchangers
• Evolution of the Na/Ca ATPase pump
• How the Autonomic Nervous System (ANS) controls ion-kinetic structures by phosphorylation and dephosphorylation
• The nature of sympathetic stimuli and parasympathetic inhibition on the ionic-molecular level
• Voltage versus ligand activation of ion channels
• The peculiar Cl- channels and their purpose during the Action Potential
• How ion channels select certain ions
• How Ca++ ions produce myocyte contraction on the ion level
• The function of the CICR
• How the CICR produces effective myocyte contraction and generates an outward Ca++ ion gradient
• The necessity of ryanodine Ca++ channels
• The tandem function of L-type and ryanodine-type Ca++ channels
• How the sarcoplasmic reticulum (SR) functions
• How the SR stores and releases Ca++ ions
• How myocytes employ Ca++ binding proteins
• The ionic-molecular function that initiates and maintains the myocyte power stroke
• Why T tubules are necessary in the myocyte yet absent from Purkinje cells
• Why myocytes need both superficial and deep cisternae
• The ionic-molecular physiology of myocyte relaxation (diastole) following contraction (systole)
• Why both the cell membrane and the sarcoplasmic reticulum need Ca++ ATPase pumps
• The functions of Na/Ca exchangers
• How and why Na/Ca exchanger function is linked to Na+ channel function
• Explanation of why Na/Ca exchanger function fluctuates during the Action Potential
• Although the cell membrane Ca++ATPase pump and the Na/Ca exchanger remove free Ca++ ions from the myocyte, most Ca++ ions go elsewhere
• Why the myocardium acts like a syncytium to conduct with negligible resistance
• Why gap junction terminology is being replaced by the more specific connexon/connexin protein model
• How gradients move ions through connexons
• The exact nature of cell-to-cell conduction
• The fascinating mechanisms of cell-to-cell depolarization
• How ion channel threshold potential perpetuates cell-to-cell conduction
• Homeostatic function of the Na/H pump and its emergency response
• How myocytes, AV node cells, and Purkinje cells depolarize
• How advancing Na+ ion waves produce the vectors of myocardial conduction
• The nature of “fast” and “slow” Na+ currents
• The anatomy, physiology, and kinetics of Na+ channel opening
• Why ion channel flow is described in terms of open probability
• Why ion channel function requires three operational states
• The necessity of closed versus inactivated ion channel status
• The specific peptide loop dynamics of fast and slow inactivation
• Why ion channels have periods of refractoriness and responsiveness
• The clinical importance of ion channel recovery from inactivation
• The ionic-molecular dynamics of repolarization
• How K+ channels repolarize the myocyte to baseline potential
• Methodology of rectification of ion channel currents; how and why
• The repolarizing K+ channels and the K+ channels that maintain baseline potential
• The teleology of the delayed-rectifier K+ channels
• The physiological reason for the extended plateau of the action potential
• IK1 function and baseline potential
• The ion-kinetic structures that participate in the plateau
• The pathophysiology of Long QT (LQT) syndromes
• Autonomic modulation via G protein intermediaries
• How autonomic function affects automaticity
• How autonomic function affects myocardial conduction and contraction
• How the autonomic nervous system (ANS) regulates AV node conduction
• Discovery of the ionic-molecular etiology of Wenckebach conduction
• ANS input via sensor-receptors provides the data for cardiac homeostasis
• How sympathetic and parasympathetic receptors modulate the function of ion-kinetic structures
• How sympathetic and parasympathetic receptors affect each other’s function
• How parasympathetic influence interferes with sympathetic phosphorylation of ion-kinetic structures
• Bouton-bouton parasympathetic inhibition of sympathetic stimulation
• Parasympathetic inhibition of sympathetic ganglia
• G protein participation in phosphorylation and dephosphorylation activity
• Adenosine – where and why it originates, and how it works
• Phospholamban and Ca++ sequestration in the sarcoplasmic reticulum
• Homeostatic parasympathetic-sympathetic interaction and interdependance
• Wenckebach conduction as vital homeostatic emergency mechanism
• How K+ channel modulation modifies the action potential and affects the heart
• The function of A1 receptors and M2 receptors
• Na/K ATPase pumps produce and maintain of K+ and Na+ gradients
• The AV node as a homeostatic necessity
• Filtering effects of the AV node
• The role of automaticity foci
• Why AV node cells lack Na+ channels, but Na+ ion influx initiates AV node depolarization
• How Ca++ channels select Ca++ ions from a sea of Na+ ions
• Ca++ channel: structural kinetics of activation
• Fast and slow inactivation kinetics of Ca++ channels
• Slow AV node conduction at the ionic-molecular level
• Calmodulin-assisted fast inactivation of Ca++ channels
• Peptide loop slow inactivation of Ca++ channels
• Sympathetic stimulation of ion-kinetic structures of AV node cells and their parasympathetic inhibition
• Parasympathetic IK(ACh) channel activation inhibits AV node conduction
• Purkinje cell conduction and the ventricular conduction system
• Ionic-molecular mechanisms that facilitate rapid conduction through Purkinje cells
• Na+ channel and Na/Ca exchanger participation in Purkinje depolarization
• Refractoriness of Purkinje cells and Mobitz AV block
• How Mobitz block at normal sinus rates or high degree Mobitz block causes dangerous bradycardia
• Purkinje repolarization and K+ channel activity
• The relation between Purkinje depolarization and conduction
• Ionic-molecular explanation of refractoriness of the ventricular conduction system
• LQT3 and Na+ channel function
• Autonomic regulation of the SA node and automaticity foci
• Autonomic sensor-receptors and SA node homeostasis
• The ion-kinetic structures of the P (pacing) cells of the SA node
• Autonomic modulation of P cell pacing
• Sympathetic/parasympathetic modulation of ion-kinetic structures of the SA node
• IK(ACh) channels and parasympathetic inhibition of the sinus pacing rate
• Ion-kinetic structures are responsible for every aspect of cardiac physiology and pathophysiology.

Ion Adventure in the Heartland, Volume I by Dale Dubin, M.D.
Hardbound, 81/2" by 11"
• 390 pages
• Profusely illustrated in full color • ISBN 0-912912-11-1 • Price $85