Responses of in vitro rat diaphragm to changes in acid-base environment

In vitro rat diaphragms initially demonstrated a decrease in the force of the twitch contraction (FC) in response to field electrode stimulation when exposed to an unbuffered increase in PCO2 (UIPCO2). These diaphragms tended to regain their initial FC upon addition of a beta-agonist even while the increased PCO2 perdured. The effect of the agonist could be reversed by propranolol. Four hemidiaphragms were bathed in a medium containing curare and exposed to UIPCO2. Their tension values were compared to the opposite sides bathed without curare and exposed to UIPCO2 of the same intensity and duration. There was no statistically significant difference in the response. Subsequently 10 rat diaphragms were each systematically challenged by UIPCO2, buffered increases in PCO2 (BIPCO2), unbuffered decreases in bicarbonate (UDHCO3), and buffered decreases in bicarbonate (BDHCO3) first without and then with isoproterenol (10(-6) M). Without isoproterenol all four challenges after 15-min exposure produced a decrease in FC, the least by BIPCO2; the largest, by UDHCO3. Upon addition of isoproterenol, FC actually increased during BIPCO2; the decreases in FC in response to UIPCO2 and UDHCO3 were abolished; the FC in response to BDHCO3 was still decreased, but less severely. The effect of the isoproterenol was not due to its following the four challenges without isoproterenol. The different magnitudes in the FC response and the presumed lack of uniform change in intracellular pH during the four challenges suggest the possibility that different components in the sarcolemma, or in the excitation-contraction coupling mechanisms responsible for the genesis of the FC are affected by the four challenges, but the nerve or neuromuscular junction may also be affected.