title: Function and clustered expression of MaxiK channels in cerebral myocytes remain intact with aging.
abstract: The incidence of stroke increases significantly in the aging population where stroke related deaths boost at >75 years and survivors are often permanently disabled. Aging is known to decrease cerebral blood flow likely due to an increase in arterial tone. Although MaxiK channels are key regulators of cerebral arterial tone their pattern of expression and function in cerebral blood vessels during aging is unknown. Using specific antibodies against the alpha-subunit of MaxiK channels and current recordings, we now demonstrate that in aging cerebral myocytes, MaxiK channels remain healthy. Furthermore, we show for the first time that in the vasculature, MaxiK channels are expressed in clusters. Clusters have an estimated radius of approximately 200 nm in young rats (3-5 month old Fisher 344 rats) which remains normal in old (25-30 month rats) cerebral myocytes. Consistent with a healthy MaxiK channel expression in old cerebral arteries, MaxiK current density, kinetics and Ca(2+) sensitivity were practically identical in young and old myocytes. Sensitivity to nanomolar concentrations of dehydrosoyasaponin-I that activates channels formed by alpha and beta subunits is also the same in young and old myocytes. These results demonstrate that MaxiK channels maintain normal expression during cerebral aging which is in sharp contrast to our previous finding of loss of expression in aging coronary arteries. It seems therefore, that cerebral myocytes have developed a protective anti-aging mechanism leading to the continued expression of MaxiK channels.
authors.affiliation: Department of Anesthesiology, Division of Molecular Medicine, David Geffen School of Medicine at University of California Los Angeles, BH-509A CHS, Box 957115, Los Angeles, CA 90095-7115, USA.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Nishimaru
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Eghbali
authors.forename: Enrico
authors.initials: E
authors.lastname: Stefani
authors.forename: Ligia
authors.initials: L
authors.lastname: Toro
mesh_terms: D000367:Age Factors; D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002536:Cerebral Arteries / Q000378:metabolism / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000032:analysis* / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D012503:Saponins / Q000378:metabolism; D014118:Toxins, Biological / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology
chemical_list: C494842:Kcnma1 protein, rat; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D024681:Potassium Channels, Calcium-Activated; D012503:Saponins; D014118:Toxins, Biological; C071764:dehydrosoyasaponin I; D009828:Oleanolic Acid; C064719:iberiotoxin; D002118:Calcium