Myocardial force generation and anoxia tolerance in the common cockle, Cerastoderma edule

The myocardium of molluscs exhibits profound anoxia tolerance, however the cellular mechanisms underlying heart performance during normoxia and anoxia are not well understood. In the present study we investigated the role of the sarcoplasmic reticulum (SR) during normoxia and chemical anoxia (2 mM sodium cyanide) in electrically paced ventricle preparations from the common cockle (Cerastoderma edule) at ~19°C. Acute anoxia caused a substantial increase in resting tension but did not significantly affect the force of contraction, rate of contraction or rate of relaxation in myocardial preparations. SR inhibition (ryanodine, 10 µM; thapsigargin, 2 µM) attenuated the increase in resting tension, and also caused a significant decrease in the force of contraction during anoxia. During normoxia, SR inhibition reduced the force and rate of contraction by 20-30 % at contraction frequencies of 0.2 Hz and 0.5 Hz. SR inhibition also elicited an increase in resting tension at 0.5 Hz. Our results suggest that the SR plays a role in maintaining cardiac performance during anoxia in cockle myocardium. Furthermore, the SR is operative during normoxia and is relatively more important in the cockle heart than in many ectothermic vertebrates. As efforts to understand the evolution of the SR are advanced, anoxia tolerant invertebrates may serve as valuable model organisms.

Myocardial force generation and anoxia tolerance in the common cockle, Cerastoderma edule

The myocardium of molluscs exhibits profound anoxia tolerance, however the cellular mechanisms underlying heart performance during normoxia and anoxia are not well understood. In the present study we investigated the role of the sarcoplasmic reticulum (SR) during normoxia and chemical anoxia (2 mM sodium cyanide) in electrically paced ventricle preparations from the common cockle (Cerastoderma edule) at ~19°C. Acute anoxia caused a substantial increase in resting tension but did not significantly affect the force of contraction, rate of contraction or rate of relaxation in myocardial preparations. SR inhibition (ryanodine, 10 µM; thapsigargin, 2 µM) attenuated the increase in resting tension, and also caused a significant decrease in the force of contraction during anoxia. During normoxia, SR inhibition reduced the force and rate of contraction by 20-30 % at contraction frequencies of 0.2 Hz and 0.5 Hz. SR inhibition also elicited an increase in resting tension at 0.5 Hz. Our results suggest that the SR plays a role in maintaining cardiac performance during anoxia in cockle myocardium. Furthermore, the SR is operative during normoxia and is relatively more important in the cockle heart than in many ectothermic vertebrates. As efforts to understand the evolution of the SR are advanced, anoxia tolerant invertebrates may serve as valuable model organisms.

Metabolic Challenge to Glia Activates an Adenosine-Mediated Safety Mechanism that Promotes Neuronal Survival by Delaying the Onset of Spreading Depression Waves

In a model of glial-specific chemical anoxia, we have examined how astrocytes influence both synaptic transmission and the viability of hippocampal pyramidal neurons. This relationship was assessed using electrophysiological, pharmacological, and biochemical techniques in rat slices and cell cultures, and oxidative metabolism was selectively impaired in glial cells by exposure to the mitochondrial gliotoxin, fluoroacetate. We found that synaptic transmission was blocked shortly after inducing glial metabolic stress and peri-infarct-like spreading depression (SD) waves developed within 1 to 2 h of treatment. Neuronal electrogenesis was not affected until SD waves developed, thereafter decaying irreversibly. The blockage of synaptic transmission was totally reversed by A1 adenosine receptor antagonists, unlike the development of SD waves, which appeared earlier under these conditions. Such blockage led to a marked reduction in the electrical viability of pyramidal neurons 1 h after gliotoxin treatment. Cell culture experiments confirmed that astrocytes indeed release adenosine. We interpret this early glial response as a novel safety mechanism that allocates metabolic resources to vital processes when the glia itself sense an energy shortage, thereby delaying or preventing entry into massive lethal ischemic-like depolarization. The implication of these results on the functional recovery of the penumbra regions after ischemic insults is discussed.