Stressor states and the cation crossroads

Karl Weber, Syamal Bhattacharya, Kevin P. Newman, Judith E. Soberman, K Ramanathan, Jesse E. McGee, Kafait Malik, William Hickerson

Research output: Contribution to journalArticle

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Abstract

Neurohormonal activation involving the hypothalamic-pituitary-adrenal axis and adrenergic nervous and renin-angiotensin-aldosterone systems is integral to stressor state–mediated homeostatic responses. The levels of effector hormones, depending upon the degree of stress, orchestrate the concordant appearance of hypokalemia, ionized hypocalcemia and hypomagnesemia, hypozincemia, and hyposelenemia. Seemingly contradictory to homeostatic responses wherein the constancy of extracellular fluid would be preserved, upregulation of cognate-binding proteins promotes coordinated translocation of cations to injured tissues, where they participate in wound healing. Associated catecholamine-mediated intracellular cation shifts regulate the equilibrium between pro-oxidants and antioxidant defenses, a critical determinant of cell survival. These acute and chronic stressor-induced iterations in extracellular and intracellular cations are collectively referred to as the cation crossroads. Intracellular cation shifts, particularly excessive accumulation of Ca2+, converge on mitochondria to induce oxidative stress and raise the opening potential of their inner membrane permeability transition pores (mPTPs). The ensuing loss of cationic homeostasis and adenosine triphosphate (ATP) production, together with osmotic swelling, leads to organellar degeneration and cellular necrosis. The overall impact of iterations in extracellular and intracellular cations and their influence on cardiac redox state, cardiomyocyte survival, and myocardial structure and function are addressed herein. Key teaching points: Acute and chronic stressor states (e.g., bodily injury and congestive heart failure, respectively) are inextricably linked to homeostatic responses, which include neurohormonal activation. Effector hormones of the hypothalamic-pituitary-adrenal axis and the adrenergic nervous and renin-angiotensin-aldosterone systems are elaborated in concert to regulate extracellular and intracellular cation concentrations. Regulatory responses converge to culminate in the contemporaneous and concordant appearance of hypokalemia, ionized hypocalcemia and hypomagnesemia, hypozincemia, and hyposelenemia, which are integral to pathophysiologic expressions of acute and chronic stressor states. The extent to which these cation concentrations decline correlates with the severity of injury and, in turn, the degree of neurohormonal activation; accordingly, they are predictive of patient prognosis. Cardiomyocytes and their mitochondria are highly susceptible to cation trafficking, including the inducibility of atrial and ventricular arrhythmias, altered cardiac redox state, threatened cardiomyocyte survival, adverse remodeling of myocardial structure by loss of cardiomyocytes and replacement with fibrous tissue, and, in turn, dysfunction of this normally efficient muscular pump. In congestive heart failure, catecholamine and parathyroid hormone–mediated cardiomyocyte calcium overloading, in particular, an adverse accumulation of mitochondrial calcium, leads to the induction of oxidative stress and increased opening potential of mitochondrial permeability transition pores with ensuing organellar degeneration and mitochondria-dependent cellular necrosis.

Original languageEnglish (US)
Pages (from-to)563-574
Number of pages12
JournalJournal of the American College of Nutrition
Volume29
Issue number6
DOIs
StatePublished - Dec 1 2010

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Cations
Cardiac Myocytes
Mitochondria
Hypokalemia
Hypocalcemia
Renin-Angiotensin System
Adrenergic Agents
Oxidation-Reduction
Catecholamines
Oxidative Stress
Necrosis
Heart Failure
Hypothalamic Hormones
Calcium
Pituitary Hormones
Extracellular Fluid
Wounds and Injuries
Wound Healing
Cardiac Arrhythmias
Permeability

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Stressor states and the cation crossroads. / Weber, Karl; Bhattacharya, Syamal; Newman, Kevin P.; Soberman, Judith E.; Ramanathan, K; McGee, Jesse E.; Malik, Kafait; Hickerson, William.

In: Journal of the American College of Nutrition, Vol. 29, No. 6, 01.12.2010, p. 563-574.

Research output: Contribution to journalArticle

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