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 α-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 ∼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 α and β 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.