tetrodotoxin and Muscle-Weakness

Saxitoxins (STX) and tetrodotoxins (TTX) are a group of chemical compounds produced by certain species of marine algae and fish. Lethal dose for a human is about 0.5-2.0 mg when the toxin enters the body via food, and 0.05 mg of poisoning at the time of injection. In the case of aerosol the lethal dose for human being is 5 mg/min/m(3). STX and TTX poisoning cause mostly symptoms from the nervous system in the form of: paresthesia around the lips, tongue, gums, distal segments of the limbs, headache, dysphonia, astigmatism, floating feeling, muscle weakness, paralysis of cranial and peripheral nerves. There is no specific antidote for STX and TTX. It is recommended supportive treatment.

Topics: Administration, Inhalation; Administration, Oral; Aerosols; Animals; Astigmatism; Biological Warfare Agents; Dysphonia; Headache; Humans; Lethal Dose 50; Muscle Weakness; Paralysis; Paresthesia; Saxitoxin; Tetrodotoxin

The biological mechanisms underlying decline in muscle power and fatigue with age are not completely understood. The contribution of alterations in the excitation-calcium release coupling in single muscle fibers was explored in this work. Single muscle fibers were voltage-clamped using the double Vaseline gap technique. The samples were obtained by needle biopsy of the vastus lateralis (quadriceps) from 9 young (25-35 years; 25.9 +/- 9.1; 5 female and 4 male) and 11 old subjects (65-75 years; 70.5 +/- 2.3; 6 f, 5 m). Data were obtained from 36 and 39 fibers from young and old subjects, respectively. Subjects included in this study had similar physical activity. Denervated and slow-twitch muscle fibers were excluded from this study. A significant reduction of maximum charge movement (Qmax) and DHP-sensitive Ca current were recorded in muscle fibers from the 65-75 group. Qmax values were 7.6 +/- 0.9 and 3.2 +/- 0.3 nC/muF for young and old muscle fibers, respectively (P < 0.01). No evidences of charge inactivation or interconversion (charge 1 to charge 2) were found. The peak Ca current was (-)4.7 +/- 0.08 and (-)2.15 +/- 0.11 muA/muF for young and old fibers, respectively (P < 0.01). The peak calcium transient studied with mag-fura-2 (400 microM) was 6.3 +/- 0.4 microM and 4.2 +/- 0.3 microM for young and old muscle fibers, respectively. Caffeine (0.5 mM) induced potentiation of the peak calcium transient in both groups. The decrease in the voltage-/Ca-dependent Ca release ratio in old fibers (0.18 +/- 0.02) compared to young fibers (0.47 +/- 0.03) (P < 0.01), was recorded in the absence of sarcoplasmic reticulum calcium depletion. These data support a significant reduction of the amount of Ca available for triggering mechanical responses in aged skeletal muscle and, the reduction of Ca release is due to DHPR-ryanodine receptor uncoupling in fast-twitch fibers. These alterations can account, at least partially for the skeletal muscle function impairment associated with aging.

Topics: Adult; Aged; Aging; Animals; Biological Transport; Biopsy, Needle; Calcium; Calcium Channels; Calcium Channels, L-Type; Female; Humans; Male; Muscle Contraction; Muscle Denervation; Muscle Fibers, Fast-Twitch; Muscle Weakness; Muscle, Skeletal; Patch-Clamp Techniques; Rats; Tetrodotoxin