Electromechanical effects of bPTH-(1-34) on rabbit sinus node cells and guinea pig papillary muscles.
The effects of bPTH-(1-34), a synthetic preparation of bovine parathyroid hormone containing the first 34 amino acids, on electromechanical activity of isolated rabbit sinus node cells and guinea pig papillary muscles were examined by microelectrode techniques. In sinus node cells, bPTH-(1-34) (10(-7) M) decreased the cycle length of spontaneous firing (SPCL) accompanied by an increase in the maximum upstroke velocity at phase 0 (dV/dtmax) without affecting the amplitude of the action potential (APA) or the maximum diastolic potential (MDP). All the effects of bPTH-(1-34) on sinus node cells were abolished by verapamil (5 X 10(-7) M), but not by pindolol (2 X 10(-7) M). In constantly driven guinea pig papillary muscles, bPTH-(1-34) caused a positive inotropic effect (+31%). The parameters of the action potential were not significantly affected. This inotropic effect of bPTH-(1-34) was inhibited by pretreatment with verapamil or a low calcium medium (0.12 mM), but was not affected by pindolol. In contrast, ryanodine (2 X 10(-6) M), an inhibitor of internal Ca2+ release, which decreased the contraction with a prolongation of the action potential duration augmented the inotropic effect of bPTH-(1-34). In papillary muscles depolarized by 26 mM [K+]O, bPTH-(1-34) enhanced the slow action potential. In voltage clamp experiments using a single sucrose-gap method, bPTH-(1-34) caused an increase in the peak amplitude of the slow inward current, while it did not affect the outward current.(ABSTRACT TRUNCATED AT 250 WORDS)
Kondo
N
N
Mitsubishi-Kasei Institute of Life Sciences, Tokyo, Japan.
Shibata
S
S
Tenner
T E
TE
Pang
P K
PK
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010869:Pindolol / Q000494:pharmacology; D011817:Rabbits; D012433:Ryanodine / Q000494:pharmacology; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects*; D019379:Teriparatide; D014700:Verapamil / Q000494:pharmacology
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D019379:Teriparatide; D012433:Ryanodine; D010869:Pindolol; D014700:Verapamil