Seasonal variations in drug response and staircase phenomena in atrial muscle from a hibernating rodent (Spermophilus richardsonii)

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Abstract
Electrically driven atrial muscle from a hibernating rodent (Spermophilus richardsonii) showed marked seasonal variations in inotropic responsiveness to both the cardiac glycoside actodigin and to raised extracellular calcium concentration. In contrast, glycoside toxicity was apparent and comparable in all tissues. These variations were accompanied by changes in force‐frequency (‘staircase’) characteristics of the tissues. In contrast, no seasonal variation was observed in either positive inotropic responses to rubidium (a non‐glycoside inhibitor of Na+ + K+ ATP‐ase) or negative inotropic responses to methacholine. In summer atria the calcium antagonist, verapamil (6 × 10−7 m) abolished the positive staircase phenomenon but did not modify the positive inotropic actions of actodigin. These data do not support the hypothesis that ‘staircase’ and glycoside‐induced inotropism are mediated through a common mechanism.